{"id":"trastuzumab","rwe":[{"pmid":"41903751","year":"2026","title":"β-glucuronidase-triggered ortho-hydroxyl-mediated cyclization strategy for the efficient delivery of phenolic payloads in antibody-drug conjugates.","finding":"","journal":"Journal of controlled release : official journal of the Controlled Release Society","studyType":"Clinical Study"},{"pmid":"41903301","year":"2026","title":"Phase Ia/Ib trial of the safety and efficacy of mobocertinib in combination with T-DM1 for patients with HER2-mutant solid tumors (WJOG16022M).","finding":"","journal":"European journal of cancer (Oxford, England : 1990)","studyType":"Clinical Study"},{"pmid":"41900890","year":"2026","title":"AXL-Driven Stemness and Hedgehog Signaling in HER2-Positive Breast Cancer with Acquired Trastuzumab Resistance: Synergistic Potential of AXL and HER2 Co-Targeting.","finding":"","journal":"Life (Basel, Switzerland)","studyType":"Clinical Study"},{"pmid":"41900869","year":"2026","title":"Analytical Physicochemical and Functional Studies to Compare AryoTrust, a Follow-On Biologics, with the Originator Trastuzumab (Herceptin).","finding":"","journal":"Pharmaceutics","studyType":"Clinical Study"},{"pmid":"41899598","year":"2026","title":"Characterization of HER2-Positive Murine Breast Cancer Models for Investigating HER2-Targeted Therapy and Immunotherapy.","finding":"","journal":"Cancers","studyType":"Clinical Study"}],"_fda":{"id":"27ab596b-f625-4866-b65a-54508ffce760","set_id":"23f3c1f4-0fc8-4804-a9e3-04cf25dd302e","openfda":{"unii":["SE2KH7T06F"],"route":["INTRAVENOUS"],"rxcui":["1658084","1658087","1658089","1658091"],"spl_id":["27ab596b-f625-4866-b65a-54508ffce760"],"brand_name":["KADCYLA"],"spl_set_id":["23f3c1f4-0fc8-4804-a9e3-04cf25dd302e"],"package_ndc":["50242-088-01","50242-087-01"],"product_ndc":["50242-087","50242-088"],"generic_name":["ADO-TRASTUZUMAB EMTANSINE"],"product_type":["HUMAN PRESCRIPTION DRUG"],"substance_name":["TRASTUZUMAB EMTANSINE"],"manufacturer_name":["Genentech, Inc."],"application_number":["BLA125427"],"is_original_packager":[true]},"version":"35","pregnancy":["8.1 Pregnancy If KADCYLA is administered during pregnancy, or if a patient becomes pregnant while receiving KADCYLA or within 7 months following the last dose of KADCYLA, health care providers and patients should immediately report KADCYLA exposure to Genentech at 1-888-835-2555. Risk Summary KADCYLA can cause fetal harm when administered to a pregnant woman. There are no available data on the use of KADCYLA in pregnant women. Cases of oligohydramnios and oligohydramnios sequence manifesting as pulmonary hypoplasia, skeletal abnormalities, and neonatal death were observed in the postmarketing setting in patients treated with trastuzumab, the antibody component of KADCYLA [see Data ] . Based on its mechanism of action, the DM1 component of KADCYLA can also cause embryo-fetal harm when administered to a pregnant woman [ see Data ]. Apprise the patient of the potential risks to a fetus. There are clinical considerations if KADCYLA is used in a pregnant woman, or if a patient becomes pregnant within 7 months following the last dose of KADCYLA [see Clinical Considerations ]. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. Clinical Considerations Fetal/Neonatal Adverse Reactions Monitor women who received KADCYLA during pregnancy or within 7 months prior to conception for oligohydramnios. If oligohydramnios occurs, perform fetal testing that is appropriate for gestational age and consistent with community standards of care. Data Human Data There are no available data on the use of KADCYLA in pregnant women. In the post-marketing setting, cases of oligohydramnios, and of oligohydramnios sequence, manifesting in the fetus as pulmonary hypoplasia, skeletal abnormalities and neonatal death were observed after treatment with trastuzumab during pregnancy. These case reports described oligohydramnios in pregnant women who received trastuzumab either alone or in combination with chemotherapy. In some case reports, amniotic fluid index increased after trastuzumab was stopped. In one case, trastuzumab therapy resumed after amniotic index improved, and oligohydramnios recurred. Animal Data There were no reproductive and developmental toxicology studies conducted with ado-trastuzumab emtansine. DM1, the cytotoxic component of KADCYLA, disrupts microtubule function. DM1 is toxic to rapidly dividing cells in animals and is genotoxic, suggesting it has the potential to cause embryotoxicity and teratogenicity. In studies where trastuzumab was administered to pregnant cynomolgus monkeys during the period of organogenesis at doses up to 25 mg/kg given twice weekly (about 7 times the clinical dose), trastuzumab crossed the placental barrier during the early (Gestation Days 20 to 50) and late (Gestation Days 120 to 150) phases of gestation. The resulting concentrations of trastuzumab in fetal serum and amniotic fluid were approximately 33% and 25%, respectively, of those present in the maternal serum but were not associated with adverse developmental effects."],"overdosage":["10 OVERDOSAGE There is no known antidote for overdose of KADCYLA. In clinical trials, overdose of KADCYLA has been reported at approximately two times the recommended dose which resulted in Grade 2 thrombocytopenia (resolved 4 days later) and one death. In the fatal case, the patient incorrectly received KADCYLA at 6 mg/kg and died approximately 3 weeks following the overdose; a cause of death and a causal relationship to KADCYLA were not established."],"references":["15 REFERENCES 1. OSHA Hazardous Drugs. OSHA . http://www.osha.gov/SLTC/hazardousdrugs/index.html"],"description":["11 DESCRIPTION KADCYLA (ado-trastuzumab emtansine) is a HER2-targeted antibody-drug conjugate (ADC) which contains the humanized anti-HER2 IgG1, trastuzumab, covalently linked to the microtubule inhibitory drug DM1 (a maytansine derivative) via the stable thioether linker MCC (4-[N-maleimidomethyl] cyclohexane-1-carboxylate). Emtansine refers to the MCC-DM1 complex. The antibody trastuzumab, is a well characterized recombinant monoclonal antibody product produced by mammalian (Chinese hamster ovary) cells, and the small molecule components (DM1 and MCC) are produced by chemical synthesis. Ado-trastuzumab emtansine contains an average of 3.5 DM1 molecules per antibody. Ado-trastuzumab emtansine has the following chemical structure: Note: The bracketed structure is DM1 plus MCC which represents the emtansine component. The n is, on average, 3.5 DM1 molecules per trastuzumab (Mab) molecule. KADCYLA (ado-trastuzumab emtansine) is a sterile, white to off-white preservative free lyophilized powder in single-dose vials. Each vial contains 100 mg or 160 mg ado-trastuzumab emtansine. Following reconstitution, each single-dose vial contains ado-trastuzumab emtansine (20 mg/mL), polysorbate 20 [0.02% (w/v)], sodium succinate (10 mM), and sucrose [6% (w/v)] with a pH of 5.0. The resulting solution containing 20 mg/mL ado-trastuzumab emtansine is administered by intravenous infusion following dilution. Chemical Structure"],"how_supplied":["16 HOW SUPPLIED/STORAGE AND HANDLING 16.1 How Supplied/Storage KADCYLA (ado-trastuzumab emtansine) is supplied as: Carton Contents NDC One 100 mg vial, single-dose vial NDC 50242-088-01 One 160 mg vial, single-dose vial NDC 50242-087-01 Store vials in a refrigerator at 2°C to 8°C (36°F to 46°F) until time of reconstitution. Do not freeze or shake. 16.2 Special Handling Follow procedures for proper handling and disposal of anticancer drugs."],"boxed_warning":["WARNING: HEPATOTOXICITY, CARDIAC TOXICITY, EMBRYO-FETAL TOXICITY Hepatotoxicity: Serious hepatotoxicity has been reported, including liver failure and death in patients treated with KADCYLA. Monitor serum transaminases and bilirubin prior to initiation of KADCYLA treatment and prior to each KADCYLA dose. Reduce dose or discontinue KADCYLA as appropriate in cases of increased serum transaminases or total bilirubin. ( 2.3 , 5.1 ) Cardiac Toxicity: KADCYLA administration may lead to reductions in left ventricular ejection fraction (LVEF). Evaluate left ventricular function in all patients prior to and during treatment with KADCYLA. Withhold treatment for clinically significant decrease in left ventricular function. ( 2.3 , 5.2 ) Embryo-Fetal Toxicity: Exposure to KADCYLA during pregnancy can result in embryo-fetal harm. Advise patients of these risks and the need for effective contraception. ( 5.3 , 8.1 , 8.3 ) WARNING: HEPATOTOXICITY, CARDIAC TOXICITY, EMBRYO-FETAL TOXICITY See full prescribing information for complete boxed warning Hepatotoxicity, liver failure and death have occurred in KADCYLA-treated patients. Monitor hepatic function prior to initiation and prior to each dose. Institute dose modifications or permanently discontinue as appropriate. ( 2.3 , 5.1 ) KADCYLA may lead to reductions in left ventricular ejection fraction (LVEF). Assess LVEF prior to initiation. Monitor and withhold dosing or discontinue as appropriate. ( 2.3 , 5.2 ) Embryo-Fetal Toxicity: Exposure to KADCYLA during pregnancy can result in embryo-fetal harm. Advise patients of these risks and the need for effective contraception. ( 5.3 , 8.1 , 8.3 )"],"geriatric_use":["8.5 Geriatric Use Of the 495 patients who were randomized to KADCYLA in EMILIA [see Clinical Studies (14.1) ] , 65 patients (13%) were ≥ 65 years of age and 11 patients (2%) were ≥ 75 years of age. In patients ≥ 65 years old (n=138 across both treatment arms) the hazard ratios for progression-free survival (PFS) and overall survival (OS) were 1.06 (95% CI: 0.68, 1.66) and 1.05 (95% CI: 0.58, 1.91), respectively. No overall differences in the safety of KADCYLA were observed in patients aged ≥ 65 compared to patients < 65 years of age. EMILIA did not include sufficient numbers of patients aged ≥ 75 years to draw conclusions on the safety or effectiveness of KADCYLA in this age group. Of the 743 patients who were randomized to KADCYLA in KATHERINE [see Clinical Studies (14.2) ] , 58 patients (8%) were ≥ 65 years of age and 2 patients (0.3%) were ≥ 75 years of age. No overall differences in the safety or effectiveness of KADCYLA were observed in patients aged ≥ 65 compared to patients < 65 years of age. KATHERINE did not include sufficient numbers of patients aged ≥ 75 years to draw conclusions on the safety or effectiveness of KADCYLA in this age group. Population pharmacokinetic analysis indicates that age does not have a clinically meaningful effect on the pharmacokinetics of ado-trastuzumab emtansine [see Clinical Pharmacology (12.3) ] ."],"pediatric_use":["8.4 Pediatric Use Safety and effectiveness of KADCYLA have not been established in pediatric patients."],"effective_time":"20260401","clinical_studies":["14 CLINICAL STUDIES 14.1 Metastatic Breast Cancer The efficacy of KADCYLA was evaluated in a randomized, multicenter, open-label trial (EMILIA) (NCT00829166) of 991 patients with HER2-positive, unresectable locally advanced or metastatic breast cancer. Prior taxane and trastuzumab-based therapy was required before trial enrollment. Patients with only prior adjuvant therapy were required to have disease recurrence during or within six months of completing adjuvant therapy. Breast tumor samples were required to show HER2 overexpression defined as 3+ IHC or FISH amplification ratio ≥ 2.0 determined at a central laboratory. Patients were randomly allocated (1:1) to receive lapatinib plus capecitabine or KADCYLA. Randomization was stratified by world region (United States, Western Europe, other), number of prior chemotherapy regimens for unresectable locally advanced or metastatic disease (0–1, > 1) and visceral versus non-visceral disease as determined by the investigators. KADCYLA was given intravenously at 3.6 mg/kg on Day 1 of a 21-day cycle. Lapatinib was administered at 1250 mg/day orally once per day of a 21-day cycle and capecitabine was administered at 1000 mg/m 2 orally twice daily on Days 1−14 of a 21-day cycle. Patients were treated with KADCYLA or lapatinib plus capecitabine until progression of disease, withdrawal of consent, or unacceptable toxicity. At the time of the primary analysis, median time on study drug was 5.7 months (range: 0–28.4) for KADCYLA, 4.9 months (range: 0–30.8) for lapatinib, and 4.8 months (range: 0–30.4) for capecitabine. The co-primary efficacy outcomes of the study were progression-free survival (PFS) based on tumor response assessments by an independent review committee (IRC), and overall survival (OS). PFS was defined as the time from the date of randomization to the date of disease progression or death from any cause (whichever occurred earlier). Overall survival was defined as the time from the date of randomization to the date of death from any cause. Additional outcomes included PFS (based on investigator tumor response assessments), objective response rate (ORR), duration of response and time to symptom progression. Patient demographics and baseline tumor characteristics were balanced between treatment arms. All patients had metastatic disease at study entry. The median age was approximately 53 years (range 24-84 years), 74% were White, 18% were Asian and 5% were Black. All but 5 patients were women. Twenty-seven percent of patients were enrolled in United States, 32% in Europe and 16% in Asia. Tumor prognostic characteristics including hormone receptor status (positive: 55%, negative: 43%), presence of visceral disease (68%) and non-visceral disease only (33%) and the number of metastatic sites (< 3: 61%, ≥ 3: 37%) were similar in the study arms. The majority of patients (88%) had received prior systemic treatment in the metastatic setting. Twelve percent of patients had prior treatment only in the neoadjuvant or adjuvant setting and had disease relapse within 6 months of treatment. All but one patient received trastuzumab prior to study entry; approximately 85% of patients received prior trastuzumab in the metastatic setting. Over 99% percent of patients had received a taxane, and 61% of patients had received an anthracycline prior to study entry. Overall, patients received a median of 3 systemic agents in the metastatic setting. Among patients with hormone receptor-positive tumors, 44.4% received prior adjuvant hormonal therapy and 44.8% received hormonal therapy for locally advanced/metastatic disease. The randomized trial demonstrated a statistically significant improvement in IRC-assessed PFS in the KADCYLA-treated group compared with the lapatinib plus capecitabine-treated group [hazard ratio (HR) = 0.65, 95% CI: 0.55, 0.77, p < 0.0001], and an increase in median PFS of 3.2 months (median PFS of 9.6 months in the KADCYLA-treated group vs. 6.4 months in the lapatinib plus capecitabine group). See Table 7 and Figure 1 . The results for investigator-assessed PFS were similar to those observed for IRC-assessed PFS. At the time of PFS analysis, 223 patients had died. More deaths occurred in the lapatinib plus capecitabine arm (26%) compared with the KADCYLA arm (19%), however the results of this interim OS analysis did not meet the pre-specified stopping boundary for statistical significance. At the time of the second interim OS analysis, 331 events had occurred. The co-primary endpoint of OS was met; OS was significantly improved in patients receiving KADCYLA (HR = 0.68, 95% CI: 0.55, 0.85, p = 0.0006). This result crossed the pre-specified efficacy stopping boundary (HR = 0.73 or p = 0.0037). The median duration of survival was 30.9 months in the KADCYLA arm vs. 25.1 months in the lapatinib plus capecitabine arm. See Table 7 and Figure 2 . A treatment benefit with KADCYLA in terms of PFS and OS was observed in patient subgroups based on stratification factors, key baseline demographic and disease characteristics, and prior treatments. In the subgroup of patients with hormone receptor-negative disease (n=426), the hazard ratios for PFS and OS were 0.56 (95% CI: 0.44, 0.72) and 0.75 (95% CI: 0.54, 1.03), respectively. In the subgroup of patients with hormone receptor-positive disease (n=545), the hazard ratios for PFS and OS were 0.72 (95% CI: 0.58, 0.91) and 0.62 (95% CI: 0.46, 0.85), respectively. In the subgroup of patients with non-measurable disease (n=205), based on IRC assessments, the hazard ratios for PFS and OS were 0.91 (95% CI: 0.59, 1.42) and 0.96 (95% CI: 0.54, 1.68), respectively; in patients with measurable disease the hazard ratios were 0.62 (95% CI: 0.52, 0.75) and 0.65 (95% CI: 0.51, 0.82), respectively. The PFS and OS hazard ratios in patients who were younger than 65 years old (n=853) were 0.62 (95% CI: 0.52, 0.74) and 0.66 (95% CI: 0.52, 0.83), respectively. In patients ≥ 65 years old (n=138), the hazard ratios for PFS and OS were 1.06 (95% CI: 0.68, 1.66) and 1.05 (95% CI: 0.58, 1.91), respectively. Table 7 Summary of Efficacy from EMILIA KADCYLA N=495 Lapatinib+Capecitabine N=496 PFS: progression-free survival; OR: objective response Progression-Free Survival (independent review) Number (%) of patients with event 265 (53.5%) 304 (61.3%) Median duration of PFS (months) 9.6 6.4 Hazard Ratio (stratified Stratified by world region (United States, Western Europe, other), number of prior chemotherapeutic regimens for locally advanced or metastatic disease (0-1 vs. > 1), and visceral vs. non-visceral disease. ) 0.650 95% CI for Hazard Ratio (0.549, 0.771) p-value (Log-Rank test, stratified ) < 0.0001 Overall Survival The second interim analysis for OS was conducted when 331 events were observed and the results are presented in this table. Number (%) of patients who died 149 (30.1%) 182 (36.7%) Median duration of survival (months) 30.9 25.1 Hazard Ratio (stratified ) 0.682 95% CI for Hazard Ratio (0.548, 0.849) p-value (Log-Rank test ) 0.0006 Objective Response Rate (independent review) Patients with measurable disease 397 389 Number of patients with OR (%) 173 (43.6%) 120 (30.8%) Difference (95% CI) 12.7% (6.0, 19.4) Duration of Objective Response (months) Number of patients with OR 173 120 Median duration (95% CI) 12.6 (8.4, 20.8) 6.5 (5.5, 7.2) Figure 1 Kaplan-Meier Curve of IRC-Assessed Progression-Free Survival for EMILIA Figure 2 Kaplan-Meier Curve of Overall Survival for EMILIA Figure 1 Figure 2 14.2 Early Breast Cancer KATHERINE (NCT01772472) was a randomized, multicenter, open-label trial of 1486 patients with HER2-positive, early breast cancer. Patients were required to have had neoadjuvant taxane and trastuzumab-based therapy with residual invasive tumor in the breast and/or axillary lymph nodes. Patients received radiotherapy and/or hormonal therapy concurrent with study treatment as per local guidelines. Breast tumor samples were required to show HER2 overexpression defined as 3+ IHC or ISH amplification ratio ≥ 2.0 determined at a central laboratory using Ventana's PATHWAY anti-HER2-/neu (4B5) Rabbit Monoclonal Primary Antibody or INFORM HER2 Dual ISH DNA Probe Cocktail assays. Patients were randomized (1:1) to receive KADCYLA or trastuzumab. Randomization was stratified by clinical stage at presentation, hormone receptor status, preoperative HER2-directed therapy (trastuzumab, trastuzumab plus additional HER2-directed agent[s]), and pathological nodal status evaluation after preoperative therapy. KADCYLA was given intravenously at 3.6 mg/kg on Day 1 of a 21-day cycle. Trastuzumab was given intravenously at 6 mg/kg on Day 1 of a 21-day cycle. Patients were treated with KADCYLA or trastuzumab for a total of 14 cycles unless there was recurrence of disease, withdrawal of consent, or unacceptable toxicity. At the time of the major efficacy outcome analysis, median treatment duration was 10 months for both KADCYLA- and trastuzumab-treated patients. Patients who discontinued KADCYLA for reasons other than disease recurrence could complete the remainder of the planned HER2-directed therapy with trastuzumab if appropriate based on toxicity considerations and investigator discretion. The major efficacy outcome of the study was invasive disease-free survival (IDFS). IDFS was defined as the time from the date of randomization to first occurrence of ipsilateral invasive breast tumor recurrence, ipsilateral local or regional invasive breast cancer recurrence, distant recurrence, contralateral invasive breast cancer, or death from any cause. Additional efficacy outcomes included IDFS including second primary non-breast cancer, disease free survival (DFS), and overall survival (OS). Patient demographics and baseline tumor characteristics were generally balanced between treatment arms. The median age was approximately 49 years (range 23-80 years), 73% were White, 9% were Asian, 6% were American Indian or Alaska Native and 3% were Black or African American. Most patients (99.7%) were women. Enrollment by region was as follows: 23% in North America, 54% in Europe and 23% throughout the rest of the world. Tumor prognostic characteristics including hormone receptor status (positive: 72%, negative: 28%), clinical stage at presentation (inoperable: 25%, operable: 75%) and pathological nodal status after preoperative therapy (node positive: 46%, node negative or not evaluated: 54%) were similar across study arms. The majority of patients (77%) had received an anthracycline-containing neoadjuvant chemotherapy regimen. Twenty percent of patients received another HER2-targeted agent in addition to trastuzumab as a component of neoadjuvant therapy; 94% of these patients received pertuzumab. A statistically significant improvement in IDFS and OS was observed in patients who received KADCYLA compared with trastuzumab. The efficacy results from KATHERINE are summarized in Table 8, Figure 3, and Figure 4 . Table 8 Efficacy Results from KATHERINE KADCYLA N=743 Trastuzumab N=743 HR: Hazard Ratio; CI: Confidence Intervals, Invasive Disease-Free Survival (IDFS) Hierarchical testing applied for IDFS and OS , Data from the pre-specified interim analysis of IDFS (67% of the number of events for the planned final analysis) with the p-value compared with the allocated alpha of 0.012 Number (%) of patients with event 91 (12.2%) 165 (22.2%) HR [95% CI] Unstratified analysis 0.50 [0.39, 0.64] p-value (Log-Rank test, unstratified) < 0.0001 3-year event-free rate 3-year event-free rate derived from Kaplan-Meier estimates , % [95% CI] 88.3 [85.8, 90.7] 77.0 [73.8, 80.7] Overall Survival (OS) , Data from the pre-specified second interim analysis of OS (82% of the number of events for the planned final analysis) with the p-value compared with the allocated alpha of 0.0263 based on the actual number of OS events at the time of the analysis Number (%) of patients with event 89 (12.0%) 126 (17.0%) HR [95% CI] 0.66 [0.51, 0.87] p-value (Log-Rank test, unstratified) 0.0027 IDFS including second primary non-breast cancer Number (%) of patients with event 95 (12.8%) 167 (22.5%) HR [95% CI] 0.51 [0.40, 0.66] 3-year event-free rate , % [95% CI] 87.7 [85.2, 90.2] 76.9 [73.7, 80.1] Disease-Free Survival (DFS) Number (%) of patients with event 98 (13.2%) 167 (22.5%) HR [95% CI] 0.53 [0.41, 0.68] 3-year event-free rate , % [95% CI] 87.4 [84.9, 89.9] 76.9 [73.7, 80.1] Figure 3 Kaplan-Meier Curve of Invasive Disease-Free Survival in KATHERINE Figure 4 Kaplan-Meier Curve of Overall Survival in KATHERINE Figure 3 Figure 4"],"pharmacodynamics":["12.2 Pharmacodynamics Cardiac Electrophysiology The effect of multiple doses of KADCYLA (3.6 mg/kg every 3 weeks) on the QTc interval was evaluated in an open label, single arm study in 51 patients with HER2-positive metastatic breast cancer. No large changes in the mean QT interval (i.e., > 20 ms) were detected in the study."],"pharmacokinetics":["12.3 Pharmacokinetics The pharmacokinetics of KADCYLA was evaluated in a phase 1 study and in a population pharmacokinetic analysis for the ado-trastuzumab emtansine conjugate (ADC) using pooled data from 5 trials in patients with breast cancer. A linear two-compartment model with first-order elimination from the central compartment adequately describes the ADC concentration-time profile. In addition to ADC, the pharmacokinetics of total antibody (conjugated and unconjugated trastuzumab), DM1 were also determined. The population pharmacokinetic analysis of ADC suggested no difference in KADCYLA exposure based on disease status (adjuvant vs. metastatic setting). The pharmacokinetics of KADCYLA are summarized below. Distribution Maximum concentrations (C max ) of ADC and DM1 were observed close to the end of infusion. In EMILIA, mean (SD) ADC and DM1 Cycle 1 C max following KADCYLA administration was 83.4 (16.5) µg/mL and 4.61 (1.61) ng/mL, respectively. In KATHERINE, mean (SD) ADC and DM1 Cycle 1 C max following KADCYLA administration was 72.6 (24.3) µg/mL and 4.71 (2.25) ng/mL, respectively. In vitro , the mean binding of DM1 to human plasma proteins was 93%. In vitro, DM1 was a substrate of P-glycoprotein (P-gp). Based on population pharmacokinetic analysis, the central volume of distribution of ADC was 3.13 L. Metabolism In vitro studies indicate that DM1, the small molecule component of KADCYLA, undergoes metabolism by CYP3A4/5. DM1 did not inhibit or induce major CYP450 enzymes in vitro. In human plasma, ado-trastuzumab emtansine catabolites MCC-DM1, Lys-MCC-DM1, and DM1 were detected at low levels. Elimination Based on population pharmacokinetic analysis, following intravenous infusion of KADCYLA, the clearance of the ADC was 0.68 L/day and the elimination half-life (t 1/2 ) was approximately 4 days. No accumulation of KADCYLA was observed after repeated dosing of intravenous infusion every 3 weeks. Based on population pharmacokinetic analysis (n=671), body weight, sum of longest diameter of target lesions by RECIST, HER2 extracellular domain (ECD) concentrations, AST, albumin, and baseline trastuzumab concentrations were identified as statistically significant covariates for ado-trastuzumab emtansine clearance. However, the magnitude of effect of these covariates on ado-trastuzumab emtansine exposure suggests that, with the exception of body weight, these covariates are unlikely to have a clinically meaningful effect on KADCYLA exposure. Therefore, the body weight based dose of 3.6 mg/kg every 3 weeks without correction for other covariates is considered appropriate. Effect of Renal Impairment Based on population pharmacokinetic analysis in 668 patients, including moderate (CLcr 30 - 59 mL/min, n=53) and mild (CLcr 60 - 89 mL/min, n=254) renal impairment, indicate that pharmacokinetics of the ADC is not affected by mild to moderate renal impairment as compared to normal renal function (CLcr ≥ 90 mL/min, n=361). Data from only one patient with severe renal impairment (CLcr < 30 mL/min) is available [see Use in Specific Populations (8.7) ] . Effect of Hepatic Impairment The liver is a primary organ for eliminating DM1 and DM1-containing catabolites. The pharmacokinetics of ado-trastuzumab emtansine and DM1-containing catabolites were evaluated after the administration of 3.6 mg/kg of KADCYLA to metastatic HER2-positive breast cancer patients with normal hepatic function (n=10), mild (Child-Pugh A; n=10) and moderate (Child-Pugh B; n=8) hepatic impairment. – Plasma concentrations of DM1 and DM1-containing catabolites (Lys-MCC-DM1 and MCC-DM1) were low and comparable between patients with and without hepatic impairment. – Systemic exposures (AUC) of ado-trastuzumab emtansine at Cycle 1 in patients with mild and moderate hepatic impairment were approximately 38% and 67% lower than that of patients with normal hepatic function, respectively. Ado-trastuzumab emtansine exposure (AUC) at Cycle 3 after repeated dosing in patients with mild or moderate hepatic dysfunction was within the range observed in patients with normal hepatic function. KADCYLA has not been studied in patients with severe hepatic impairment (Child-Pugh class C). Effects of Age and Race Based on population pharmacokinetic analysis, age (< 65 [n=577]; 65 - 75 (n=78); > 75 [n=16]) and race (Asian [n=73]; non-Asian [n=598]) do not have a clinically meaningful effect on the pharmacokinetics of ado-trastuzumab emtansine."],"adverse_reactions":["6 ADVERSE REACTIONS The following adverse reactions are discussed in greater detail in other sections of the label: Hepatotoxicity [See Warnings and Precautions (5.1) ] Left Ventricular Dysfunction [See Warnings and Precautions (5.2) ] Embryo-Fetal Toxicity [See Warnings and Precautions (5.3) ] Pulmonary Toxicity [See Warnings and Precautions (5.4) ] Infusion-Related Reactions, Hypersensitivity Reactions [See Warnings and Precautions (5.5) ] Hemorrhage [See Warnings and Precautions (5.6) ] Thrombocytopenia [See Warnings and Precautions (5.7) ] Neurotoxicity [See Warnings and Precautions (5.8) ] Metastatic Breast Cancer The most common adverse reactions (≥ 25%) with KADCYLA were fatigue, nausea, musculoskeletal pain, hemorrhage, thrombocytopenia, headache, increased transaminases, constipation and epistaxis. ( 6.1 ) Early Breast Cancer The most common adverse reactions (≥ 25%) with KADCYLA were fatigue, nausea, increased transaminases, musculoskeletal pain, hemorrhage, thrombocytopenia, headache, peripheral neuropathy, and arthralgia. To report SUSPECTED ADVERSE REACTIONS, contact Genentech at 1-888-835-2555 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The data in the WARNINGS AND PRECAUTIONS reflect exposure to KADCYLA as a single agent at 3.6 mg/kg given as an intravenous infusion every 3 weeks (21-day cycle) in 1624 patients including 884 patients with HER2-positive metastatic breast cancer and 740 patients with HER2-positive early breast cancer (KATHERINE trial). Metastatic Breast Cancer In clinical trials, KADCYLA has been evaluated as single-agent in 884 patients with HER2-positive metastatic breast cancer. The most common (≥ 25%) adverse reactions were fatigue, nausea, musculoskeletal pain, hemorrhage, thrombocytopenia, headache, increased transaminases, constipation and epistaxis. The adverse reactions described in Table 3 were identified in patients with HER2-positive metastatic breast cancer treated in the EMILIA trial [see Clinical Studies (14.1) ] . Patients were randomized to receive KADCYLA or lapatinib plus capecitabine. The median duration of study treatment was 7.6 months for patients in the KADCYLA-treated group and 5.5 months and 5.3 months for patients treated with lapatinib and capecitabine, respectively. In the EMILIA trial, 43% of patients experienced Grade ≥ 3 adverse reactions in the KADCYLA-treated group compared with 59% of patients in the lapatinib plus capecitabine-treated group. Dose adjustments for KADCYLA were permitted [see Dosage and Administration (2.2) ] . Thirty-two patients (7%) discontinued KADCYLA due to an adverse reaction, compared with 41 patients (8%) who discontinued lapatinib, and 51 patients (10%) who discontinued capecitabine due to an adverse reaction. The most common adverse reactions leading to KADCYLA discontinuation were thrombocytopenia and increased transaminases. Eighty patients (16%) treated with KADCYLA had adverse reactions leading to dose reductions. The most frequent adverse reactions leading to dose reduction of KADCYLA (in ≥ 1% of patients) included thrombocytopenia, increased transaminases, and peripheral neuropathy. Adverse reactions that led to dose delays occurred in 116 (24%) of KADCYLA treated patients. The most frequent adverse reactions leading to a dose delay of KADCYLA (in ≥ 1% of patients) were neutropenia, thrombocytopenia, leukopenia, fatigue, increased transaminases and pyrexia. Table 3 reports the adverse reactions that occurred in patients in the KADCYLA-treated group (n=490) of the EMILIA trial. Selected laboratory abnormalities are shown in Table 4 . The most common adverse reactions seen with KADCYLA in the randomized trial (frequency > 25%) were nausea, fatigue, musculoskeletal pain, hemorrhage, thrombocytopenia, increased transaminases, headache, and constipation. The most common NCI–CTCAE (version 3) Grade ≥ 3 adverse reactions (frequency > 2%) were thrombocytopenia, increased transaminases, anemia, hypokalemia, peripheral neuropathy and fatigue. Table 3 Adverse Reactions Occurring in ≥ 10% of Patients on the KADCYLA Treatment Arm in the EMILIA Trial Grouped terms were used for the following Adverse Reactions: Thrombocytopenia: thrombocytopenia, platelet count decreased Anemia: anemia, hemoglobin decreased Abdominal pain: abdominal pain, abdominal pain upper Stomatitis: stomatitis, mucosal inflammation, oropharyngeal pain Transaminases Increased: transaminases increased, aspartate aminotransferase increased, alanine aminotransferase increased, gamma-glutamyltransferase increased, liver function test abnormal, hepatic enzyme increased, hepatic function abnormal Hypokalemia: hypokalemia, blood potassium decreased Musculoskeletal Pain: muscle spasms, musculoskeletal discomfort, musculoskeletal chest pain, back pain, pain in extremity, bone pain, musculoskeletal pain Peripheral neuropathy: neuropathy peripheral, peripheral sensory neuropathy, peripheral motor neuropathy, paresthesia Hemorrhage: Hemorrhage terms (excl laboratory terms) (SMQ, wide), Hemorrhage laboratory terms (SMQ, narrow). Adverse Reactions KADCYLA (3.6 mg/kg) n=490 Lapatinib (1250 mg) + Capecitabine (2000 mg/m 2 ) n=488 All Grades (%) Grade 3 – 4 (%) All Grades (%) Grade 3 – 4 (%) SMQ=standardized MedDRA queries Blood and Lymphatic System Disorders Thrombocytopenia 31 15 3.3 0.4 Anemia 14 4.1 11 2.5 Gastrointestinal Disorders Nausea 40 0.8 45 2.5 Constipation 27 0.4 11 0 Diarrhea 24 1.6 80 21 Vomiting 19 0.8 30 4.5 Abdominal pain 19 0.8 18 1.6 Dry Mouth 17 0 4.9 0.2 Stomatitis 14 0.2 33 2.5 General Disorders and Administration Fatigue 36 2.5 28 3.5 Pyrexia 19 0.2 8 0.4 Asthenia 18 0.4 18 1.6 Investigations Transaminases increased 29 8.0 14 2.5 Metabolism and Nutrition Disorders Hypokalemia 10 2.7 9 4.7 Musculoskeletal and Connective Tissue Disorders Musculoskeletal pain 36 1.8 31 1.4 Arthralgia 19 0.6 8 0 Myalgia 14 0.6 3.7 0 Nervous System Disorders Headache 28 0.8 15 0.8 Peripheral neuropathy 21 2.2 14 0.2 Dizziness 10 0.4 11 0.2 Psychiatric Disorders Insomnia 12 0.4 9 0.2 Respiratory, Thoracic, and Mediastinal Disorders Epistaxis 23 0.2 8 0 Cough 18 0.2 13 0.2 Dyspnea 12 0.8 8 0.4 Skin and Subcutaneous Tissue Disorders Rash 12 0 28 1.8 Vascular Disorders Hemorrhage 32 1.8 16 0.8 The following clinically relevant adverse reactions were reported in < 10% of patients in the KADCYLA-treated group in EMILIA: dyspepsia (9%), urinary tract infection (9%), chills (8%), dysgeusia (8%), neutropenia (7%), peripheral edema (7%), pruritus (6%), hypertension (5%), blood alkaline phosphatase increased (4.7%), vision blurred (4.5%), conjunctivitis (3.9%), dry eye (3.9%), lacrimation increased (3.3%), drug hypersensitivity (2.2%), left ventricular dysfunction (1.8%), infusion-related reaction (1.4%), pneumonitis (1.2%), nodular regenerative hyperplasia (0.4%), portal hypertension (0.4%). Table 4 Selected Laboratory Abnormalities (EMILIA) Parameter KADCYLA (3.6 mg/kg) Lapatinib (1250 mg) + Capecitabine (2000 mg/m 2 ) All Grades (%) Grade 3 (%) Grade 4 (%) All Grades (%) Grade 3 (%) Grade 4 (%) Chemistry Increased AST 98 7 0.5 65 3 0 Increased ALT 82 5 0.2 54 3 0 Decreased potassium 33 3 0 31 6 0.8 Increased bilirubin 17 0.6 0 57 2 0 Hematology Decreased platelet count 83 14 3 21 0.4 0.6 Decreased hemoglobin 60 4 1 64 3 0.2 Decreased neutrophils 39 3 0.6 38 6 2 Early Breast Cancer KADCYLA has been evaluated as a single-agent in 740 patients with HER2-positive early breast cancer. The adverse reactions described in Table 5 were identified in patients with HER2-positive early breast cancer treated in the KATHERINE trial [see Clinical Studies (14.2) ] . Patients were randomized to receive KADCYLA or trastuzumab. The median duration of study treatment was 10 months for patients in the KADCYLA-treated group and 10 months for patients treated with trastuzumab. One hundred and ninety (26%) patients experienced Grade ≥ 3 adverse reactions in the KADCYLA-treated group compared with 111 (15%) patients in the trastuzumab group. One hundred and thirty-three patients (18%) discontinued KADCYLA due to an adverse reaction, compared with 15 patients (2.1%) who discontinued trastuzumab due to an adverse reaction. The most common adverse reactions leading to KADCYLA discontinuation (in ≥ 1% of patients) were platelet count decreased, blood bilirubin increased, ejection fraction decreased, AST increased, ALT increased, and peripheral neuropathy. Dose adjustments for KADCYLA were permitted [see Dosage and Administration (2.2) ] . One hundred and six patients (14%) treated with KADCYLA had dose reductions. The most frequent adverse reactions leading to dose reduction of KADCYLA (in ≥ 1% of patients) included thrombocytopenia, increased transaminases, blood bilirubin and fatigue. Adverse reactions that led to dose delays occurred in 106 (14%) of KADCYLA treated patients. The most frequent adverse reactions leading to a dose delay of KADCYLA (in ≥ 1% of patients) were neutropenia, thrombocytopenia and AST increased. Selected laboratory abnormalities are shown in Table 6 . The most common adverse reactions seen with KADCYLA in the randomized trial (frequency > 25%) were fatigue, nausea, increased transaminases, musculoskeletal pain, hemorrhage, thrombocytopenia, headache, peripheral neuropathy, and arthralgia. The most common NCI–CTCAE (version 3) Grade ≥ 3 adverse reactions (> 2%) were thrombocytopenia and hypertension. Table 5 Adverse Reactions Occurring in ≥ 10% of Patients in the KATHERINE Trial Grouped terms were used for the following Adverse Reactions: Thrombocytopenia: thrombocytopenia, platelet count decreased Anemia: anemia, hemoglobin decreased Stomatitis: stomatitis, mucosal inflammation, oropharyngeal pain Abdominal pain: abdominal pain, abdominal pain upper Urinary Tract Infection: urinary tract infection, cystitis Transaminases Increased: transaminases increased, aspartate aminotransferase increased, alanine aminotransferase increased, gamma-glutamyltransferase increased, liver function test abnormal, hepatic enzyme increased, hepatic function abnormal Musculoskeletal Pain: muscle spasms, musculoskeletal discomfort, musculoskeletal chest pain, back pain, pain in extremity, bone pain, musculoskeletal pain Peripheral neuropathy: neuropathy peripheral, peripheral sensory neuropathy, peripheral motor neuropathy, paresthesia Hemorrhage: Hemorrhage terms (excl laboratory terms) (SMQ, wide), Hemorrhage laboratory terms (SMQ, narrow) Adverse Reactions KADCYLA n=740 Trastuzumab n=720 All grades (%) Grade 3 – 4 (%) All grades (%) Grade 3 – 4 (%) SMQ=standardized MedDRA queries Blood and Lymphatic System Disorders Thrombocytopenia 29 6 2.4 0.3 Anemia 10 1.1 9 0.1 Gastrointestinal Disorders Nausea 42 0.5 13 0.3 Constipation 17 0.1 8 0 Stomatitis 15 0.1 8 0.1 Vomiting 15 0.5 5 0.3 Dry Mouth 14 0.1 1.3 0 Diarrhea 12 0.8 13 0.3 Abdominal pain 11 0.4 7 0.3 General Disorders and Administration Fatigue 50 1.1 34 0.1 Pyrexia 10 0 4 0 Infections and Infestations Urinary tract infection 10 0.3 6 0.1 Investigations Transaminases increased 32 1.5 8 0.4 Musculoskeletal and Connective Tissue Disorders Musculoskeletal pain 30 0.7 29 0.7 Arthralgia 26 0.1 21 0 Myalgia 15 0.4 11 0 Nervous System Disorders Headache 28 0 17 0.1 Peripheral neuropathy 28 1.6 14 0.1 Dizziness 10 0.1 8 0.3 Psychiatric Disorders Insomnia 14 0 12 0.1 Respiratory, Thoracic, and Mediastinal Disorders Epistaxis 22 0 3.5 0 Cough 14 0.1 12 0 Vascular Disorders Hemorrhage 29 0.4 Included one fatal hemorrhage. 10 0.3 The following clinically relevant adverse reactions were reported in < 10% of patients in the KADCYLA-treated group in KATHERINE: blood alkaline phosphatase increased (8%), dysgeusia (8%), dyspnea (8%), neutropenia (8%), blood bilirubin increased (7%), hypokalemia (7%), pruritus (7%), hypertension (6%), lacrimation increased (6%), chills (5%), dry eye (4.5%), dyspepsia (4.3%), peripheral edema (3.9%),vision blurred (3.9%), conjunctivitis (3.5%), left ventricular dysfunction (3.0%), drug hypersensitivity (2.7%), infusion-related reaction (1.6%), radiation pneumonitis (1.5%), pneumonitis (1.1%), rash (1.1%), asthenia (0.4%), nodular regenerative hyperplasia (0.3%). Table 6 Selected Laboratory Abnormalities (KATHERINE) Parameter KADCYLA n=740 Trastuzumab n=720 All Grade (%) Grade 3 (%) Grade 4 (%) All Grade (%) Grade 3 (%) Grade 4 (%) Chemistry Increased AST 79 0.8 0 21 0.1 0 Increased ALT 55 0.7 0 21 0.1 0 Decreased potassium 26 2 0.5 9 0.7 0.1 Increased bilirubin 12 0 0 4 0.7 0 Hematology Decreased platelet count 51 4 2 13 0.1 0.1 Decreased hemoglobin 31 1 0 29 0.3 0 Decreased neutrophils 24 1 0 19 0.6 0.6 6.2 Post-Marketing Experience The following adverse reactions have been identified during post-approval use of KADCYLA. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Adverse Reactions from Observational Studies CHF and > 10% reduction in LVEF in patients with HER2-positive metastatic breast cancer with a baseline LVEF of 40-49% treated with KADCYLA [see Warnings and Precautions (5.2) ] . Adverse Reactions from Postmarketing Spontaneous Reports Tumor lysis syndrome (TLS) Skin/tissue necrosis after extravasation"],"contraindications":["4 CONTRAINDICATIONS None. None. ( 4 )"],"drug_interactions":["7 DRUG INTERACTIONS No formal drug-drug interaction studies with KADCYLA have been conducted. In vitro studies indicate that DM1, the cytotoxic component of KADCYLA, is metabolized mainly by CYP3A4 and to a lesser extent by CYP3A5. Concomitant use of strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, clarithromycin, atazanavir, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, and voriconazole) with KADCYLA should be avoided due to the potential for an increase in DM1 exposure and toxicity. Consider an alternate medication with no or minimal potential to inhibit CYP3A4. If concomitant use of strong CYP3A4 inhibitors is unavoidable, consider delaying KADCYLA treatment until the strong CYP3A4 inhibitors have cleared from the circulation (approximately 3 elimination half-lives of the inhibitors) when possible. If a strong CYP3A4 inhibitor is coadministered and KADCYLA treatment cannot be delayed, patients should be closely monitored for adverse reactions."],"how_supplied_table":["
Carton ContentsNDC
One 100 mg vial, single-dose vialNDC 50242-088-01
One 160 mg vial, single-dose vialNDC 50242-087-01
"],"mechanism_of_action":["12.1 Mechanism of Action Ado-trastuzumab emtansine is a HER2-targeted antibody-drug conjugate. The antibody is the humanized anti-HER2 IgG1, trastuzumab. The small molecule cytotoxin, DM1, is a microtubule inhibitor. Upon binding to sub-domain IV of the HER2 receptor, ado-trastuzumab emtansine undergoes receptor-mediated internalization and subsequent lysosomal degradation, resulting in intracellular release of DM1-containing cytotoxic catabolites. Binding of DM1 to tubulin disrupts microtubule networks in the cell, which results in cell cycle arrest and apoptotic cell death. In addition, in vitro studies have shown that similar to trastuzumab, ado-trastuzumab emtansine inhibits HER2 receptor signaling, mediates antibody-dependent cell-mediated cytotoxicity and inhibits shedding of the HER2 extracellular domain in human breast cancer cells that overexpress HER2."],"recent_major_changes":["Dosage and Administration ( 2.4 ) 03/2026"],"storage_and_handling":["16.1 How Supplied/Storage KADCYLA (ado-trastuzumab emtansine) is supplied as: Carton Contents NDC One 100 mg vial, single-dose vial NDC 50242-088-01 One 160 mg vial, single-dose vial NDC 50242-087-01 Store vials in a refrigerator at 2°C to 8°C (36°F to 46°F) until time of reconstitution. Do not freeze or shake."],"clinical_pharmacology":["12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Ado-trastuzumab emtansine is a HER2-targeted antibody-drug conjugate. The antibody is the humanized anti-HER2 IgG1, trastuzumab. The small molecule cytotoxin, DM1, is a microtubule inhibitor. Upon binding to sub-domain IV of the HER2 receptor, ado-trastuzumab emtansine undergoes receptor-mediated internalization and subsequent lysosomal degradation, resulting in intracellular release of DM1-containing cytotoxic catabolites. Binding of DM1 to tubulin disrupts microtubule networks in the cell, which results in cell cycle arrest and apoptotic cell death. In addition, in vitro studies have shown that similar to trastuzumab, ado-trastuzumab emtansine inhibits HER2 receptor signaling, mediates antibody-dependent cell-mediated cytotoxicity and inhibits shedding of the HER2 extracellular domain in human breast cancer cells that overexpress HER2. 12.2 Pharmacodynamics Cardiac Electrophysiology The effect of multiple doses of KADCYLA (3.6 mg/kg every 3 weeks) on the QTc interval was evaluated in an open label, single arm study in 51 patients with HER2-positive metastatic breast cancer. No large changes in the mean QT interval (i.e., > 20 ms) were detected in the study. 12.3 Pharmacokinetics The pharmacokinetics of KADCYLA was evaluated in a phase 1 study and in a population pharmacokinetic analysis for the ado-trastuzumab emtansine conjugate (ADC) using pooled data from 5 trials in patients with breast cancer. A linear two-compartment model with first-order elimination from the central compartment adequately describes the ADC concentration-time profile. In addition to ADC, the pharmacokinetics of total antibody (conjugated and unconjugated trastuzumab), DM1 were also determined. The population pharmacokinetic analysis of ADC suggested no difference in KADCYLA exposure based on disease status (adjuvant vs. metastatic setting). The pharmacokinetics of KADCYLA are summarized below. Distribution Maximum concentrations (C max ) of ADC and DM1 were observed close to the end of infusion. In EMILIA, mean (SD) ADC and DM1 Cycle 1 C max following KADCYLA administration was 83.4 (16.5) µg/mL and 4.61 (1.61) ng/mL, respectively. In KATHERINE, mean (SD) ADC and DM1 Cycle 1 C max following KADCYLA administration was 72.6 (24.3) µg/mL and 4.71 (2.25) ng/mL, respectively. In vitro , the mean binding of DM1 to human plasma proteins was 93%. In vitro, DM1 was a substrate of P-glycoprotein (P-gp). Based on population pharmacokinetic analysis, the central volume of distribution of ADC was 3.13 L. Metabolism In vitro studies indicate that DM1, the small molecule component of KADCYLA, undergoes metabolism by CYP3A4/5. DM1 did not inhibit or induce major CYP450 enzymes in vitro. In human plasma, ado-trastuzumab emtansine catabolites MCC-DM1, Lys-MCC-DM1, and DM1 were detected at low levels. Elimination Based on population pharmacokinetic analysis, following intravenous infusion of KADCYLA, the clearance of the ADC was 0.68 L/day and the elimination half-life (t 1/2 ) was approximately 4 days. No accumulation of KADCYLA was observed after repeated dosing of intravenous infusion every 3 weeks. Based on population pharmacokinetic analysis (n=671), body weight, sum of longest diameter of target lesions by RECIST, HER2 extracellular domain (ECD) concentrations, AST, albumin, and baseline trastuzumab concentrations were identified as statistically significant covariates for ado-trastuzumab emtansine clearance. However, the magnitude of effect of these covariates on ado-trastuzumab emtansine exposure suggests that, with the exception of body weight, these covariates are unlikely to have a clinically meaningful effect on KADCYLA exposure. Therefore, the body weight based dose of 3.6 mg/kg every 3 weeks without correction for other covariates is considered appropriate. Effect of Renal Impairment Based on population pharmacokinetic analysis in 668 patients, including moderate (CLcr 30 - 59 mL/min, n=53) and mild (CLcr 60 - 89 mL/min, n=254) renal impairment, indicate that pharmacokinetics of the ADC is not affected by mild to moderate renal impairment as compared to normal renal function (CLcr ≥ 90 mL/min, n=361). Data from only one patient with severe renal impairment (CLcr < 30 mL/min) is available [see Use in Specific Populations (8.7) ] . Effect of Hepatic Impairment The liver is a primary organ for eliminating DM1 and DM1-containing catabolites. The pharmacokinetics of ado-trastuzumab emtansine and DM1-containing catabolites were evaluated after the administration of 3.6 mg/kg of KADCYLA to metastatic HER2-positive breast cancer patients with normal hepatic function (n=10), mild (Child-Pugh A; n=10) and moderate (Child-Pugh B; n=8) hepatic impairment. – Plasma concentrations of DM1 and DM1-containing catabolites (Lys-MCC-DM1 and MCC-DM1) were low and comparable between patients with and without hepatic impairment. – Systemic exposures (AUC) of ado-trastuzumab emtansine at Cycle 1 in patients with mild and moderate hepatic impairment were approximately 38% and 67% lower than that of patients with normal hepatic function, respectively. Ado-trastuzumab emtansine exposure (AUC) at Cycle 3 after repeated dosing in patients with mild or moderate hepatic dysfunction was within the range observed in patients with normal hepatic function. KADCYLA has not been studied in patients with severe hepatic impairment (Child-Pugh class C). Effects of Age and Race Based on population pharmacokinetic analysis, age (< 65 [n=577]; 65 - 75 (n=78); > 75 [n=16]) and race (Asian [n=73]; non-Asian [n=598]) do not have a clinically meaningful effect on the pharmacokinetics of ado-trastuzumab emtansine. 12.6 Immunogenicity The observed incidence of anti-drug antibodies (ADA) is highly dependent on the sensitivity and specificity of the assay. Differences in assay methods preclude meaningful comparisons of the incidence of ADA in the studies described below with the incidence of ADA in other studies, including those of ado-trastuzumab emtansine or of other ado-trastuzumab emtansine products. Among patients who received KADCYLA as a single agent for a median duration of 10 months in seven clinical trials, 5% (64/1243) of patients tested positive for antibodies against ado-trastuzumab emtansine at one or more post-dose timepoints. Neutralizing antibodies against ado-trastuzumab emtansine were detected in 45% (18/40) of evaluable patients who were ADA positive. Because of the low occurrence of ADA, the effect of these antibodies on the pharmacokinetics, pharmacodynamics, safety, and/or effectiveness of ado-trastuzumab emtansine is unknown. The presence of ado-trastuzumab emtansine in patient serum at the time of ADA sampling may interfere with the ability of this assay to detect anti-ado-trastuzumab emtansine antibodies. As a result, data may not accurately reflect the true incidence of anti-ado-trastuzumab emtansine antibody development."],"indications_and_usage":["1 INDICATIONS AND USAGE KADCYLA is a HER2-targeted antibody and microtubule inhibitor conjugate indicated, as a single agent, for: the treatment of patients with HER2-positive, metastatic breast cancer who previously received trastuzumab and a taxane, separately or in combination. Patients should have either: received prior therapy for metastatic disease, or developed disease recurrence during or within six months of completing adjuvant therapy. ( 1.1 ) the adjuvant treatment of patients with HER2-positive early breast cancer who have residual invasive disease after neoadjuvant taxane and trastuzumab-based treatment. ( 1.2 ) Select patients for therapy based on an FDA-authorized test for KADCYLA [see Dosage and Administration (2.1) ] 1.1 Metastatic Breast Cancer (MBC) KADCYLA ® , as a single agent, is indicated for the treatment of patients with HER2-positive, metastatic breast cancer who previously received trastuzumab and a taxane, separately or in combination. Patients should have either: Received prior therapy for metastatic disease, or Developed disease recurrence during or within six months of completing adjuvant therapy. Select patients for therapy based on an FDA-authorized test for KADCYLA [ see Dosage and Administration (2.1) ]. 1.2 Early Breast Cancer (EBC) KADCYLA, as a single agent, is indicated for the adjuvant treatment of patients with HER2-positive early breast cancer who have residual invasive disease after neoadjuvant taxane and trastuzumab -based treatment. Select patients for therapy based on an FDA-authorized test for KADCYLA [ see Dosage and Administration (2.1) ]."],"warnings_and_cautions":["5 WARNINGS AND PRECAUTIONS Pulmonary Toxicity: Permanently discontinue KADCYLA in patients diagnosed with interstitial lung disease or pneumonitis. For patients with radiation pneumonitis in the adjuvant setting, permanently discontinue KADCYLA for Grade ≥ 3 or for Grade 2 not responding to standard treatment. ( 2.2 , 5.4 ) Infusion-Related Reactions, Hypersensitivity Reactions: Monitor for signs and symptoms during and after infusion. If significant infusion-related reactions or hypersensitivity reactions occur, slow or interrupt the infusion and administer appropriate medical therapies. Permanently discontinue KADCYLA for life threatening infusion-related reaction. ( 2.1 , 2.2 , 5.5 ) Hemorrhage: Fatal cases of hemorrhage occurred in clinical trials among patients with no known identified risk factors, as well as among patients with thrombocytopenia and those receiving anti-coagulation and antiplatelet therapy. Use caution with these agents and consider additional monitoring when concomitant use is medically necessary . ( 5.6 ) Thrombocytopenia: Monitor platelet counts prior to each KADCYLA dose. Institute dose modifications as appropriate. ( 2.2 , 5.7 ) Neurotoxicity: Monitor for signs or symptoms. Withhold dosing temporarily for patients experiencing Grade 3 or 4 peripheral neuropathy. ( 2.2 , 5.8 , 13.2 ) 5.1 Hepatotoxicity Hepatotoxicity, predominantly in the form of asymptomatic, transient increases in the concentrations of serum transaminases, has been observed in clinical trials with KADCYLA [see Adverse Reactions (6.1) ] . Serious hepatotoxicity, including 3 fatal cases, has been observed in clinical trials (n=1624) with KADCYLA as single-agent. All fatal cases occurred in MBC clinical trials with KADCYLA, which included severe drug-induced liver injury and associated hepatic encephalopathy. Some of the patients experiencing hepatotoxicity had comorbidities and/or concomitant medications with known hepatotoxic potential. Monitor serum transaminases and bilirubin prior to initiation of KADCYLA treatment and prior to each KADCYLA dose. Patients with known active liver disease (such as, hepatitis B virus or hepatitis C virus) were excluded from the EMILIA and KATHERINE studies [see Clinical Studies (14.1) ] . Reduce the dose or discontinue KADCYLA as appropriate in cases of increased serum transaminases and/or total bilirubin [see Dosage and Administration (2.2) ] . Permanently discontinue KADCYLA treatment in patients with serum transaminases > 3 × ULN and concomitant total bilirubin > 2 × ULN. KADCYLA has not been studied in patients with serum transaminases > 2.5 × ULN or bilirubin > 1.5 × ULN prior to the initiation of treatment. In clinical trials of KADCYLA, cases of nodular regenerative hyperplasia (NRH) of the liver have been identified from liver biopsies (5 cases out of 1624 treated patients, one of which was fatal). Two of these five cases of NRH were observed in EMILIA and two were observed in KATHERINE [see Adverse Reactions (6.1) ] . NRH is a rare liver condition characterized by widespread benign transformation of hepatic parenchyma into small regenerative nodules; NRH may lead to non-cirrhotic portal hypertension. The diagnosis of NRH can be confirmed only by histopathology. NRH should be considered in all patients with clinical symptoms of portal hypertension and/or cirrhosis-like pattern seen on the computed tomography (CT) scan of the liver but with normal transaminases and no other manifestations of cirrhosis. Upon diagnosis of NRH, KADCYLA treatment must be permanently discontinued. 5.2 Left Ventricular Dysfunction Patients treated with KADCYLA are at increased risk of developing left ventricular dysfunction. A decrease of LVEF to < 40% has been observed in patients treated with KADCYLA. Serious cases of heart failure, with no fatal cases, have been observed in clinical trials with KADCYLA. In EMILIA, left ventricular dysfunction occurred in 1.8% of patients in the KADCYLA-treated group and 3.3% of patients in the lapatinib plus capecitabine-treated group. In KATHERINE, left ventricular dysfunction occurred in 0.4% of patients in the KADCYLA-treated group and 0.6% of patients in the trastuzumab-treated group [see Adverse Reactions (6.1) ] . Based on limited data from a retrospective observational study, 22% (7 of 32) of patients with HER2-positive metastatic breast cancer (MBC) with a baseline LVEF of 40-49% treated with KADCYLA developed a congestive heart failure (CHF) or a > 10% reduction in LVEF [see Adverse Reactions (6.2) ]. Assess LVEF prior to initiation of KADCYLA and at regular intervals (e.g. every three months) during treatment to ensure the LVEF is within the institution's normal limits. KADCYLA has not been studied in an adequately controlled study in patients with LVEF < 50%. For patients with MBC, if, at routine monitoring, LVEF is < 40%, or is 40% to 45% with a 10% or greater absolute decrease below the pretreatment value, withhold KADCYLA and repeat LVEF assessment within approximately 3 weeks. Permanently discontinue KADCYLA if the LVEF has not improved or has declined further. For patients with EBC, if, at routine monitoring, LVEF is < 45%, or is 45% to 49% with a 10% or greater absolute decrease below the pretreatment value, withhold KADCYLA and repeat LVEF assessment within approximately 3 weeks. Permanently discontinue KADCYLA if the LVEF has not improved or has declined further [see Dosage and Administration (2.2) ] . Patients with a history of symptomatic CHF, serious cardiac arrhythmia, or history of myocardial infarction or unstable angina within 6 months were excluded from the EMILIA and KATHERINE studies [see Clinical Studies (14.1) ] . 5.3 Embryo-Fetal Toxicity KADCYLA can cause fetal harm when administered to a pregnant woman. Cases of oligohydramnios, and oligohydramnios sequence manifesting as pulmonary hypoplasia, skeletal abnormalities and neonatal death were observed in the post-marketing setting in patients treated with trastuzumab, the antibody component of KADCYLA. DM1, the cytotoxic component of KADCYLA, can cause embryo-fetal toxicity based on its mechanism of action. Verify the pregnancy status of females of reproductive potential prior to the initiation of KADCYLA. Advise pregnant women and females of reproductive potential that exposure to KADCYLA during pregnancy or within 7 months prior to conception can result in fetal harm. Advise females of reproductive potential to use effective contraception during treatment and for 7 months following the last dose of KADCYLA [see Use in Specific Populations (8.1 , 8.3) ]. 5.4 Pulmonary Toxicity Cases of interstitial lung disease (ILD), including pneumonitis, some leading to acute respiratory distress syndrome or fatal outcome have been reported in clinical trials with KADCYLA. Signs and symptoms include dyspnea, cough, fatigue, and pulmonary infiltrates. In patients with MBC, pneumonitis was reported at an incidence of 0.8% (7 out of 884 treated patients), with one case of Grade 3 pneumonitis. The overall incidence of pneumonitis was 1.2% in EMILIA. In KATHERINE, pneumonitis was reported at an incidence of 1.1% (8 out of 740 patients treated with KADCYLA), with one case of Grade 3 pneumonitis. Radiation pneumonitis was reported at an incidence of 1.8% (11 out of 623 patients treated with adjuvant radiotherapy and KADCYLA), with 2 cases of Grade 3 radiation pneumonitis [see Adverse Reactions (6.1) ] . Permanently discontinue treatment with KADCYLA in patients diagnosed with ILD or pneumonitis. For patients with radiation pneumonitis in the adjuvant setting, KADCYLA should be permanently discontinued for Grade ≥ 3 or for Grade 2 not responding to standard treatment [see Dose Modifications (2.3) ] . Patients with dyspnea at rest due to complications of advanced malignancy, co-morbidities, and receiving concurrent pulmonary radiation therapy may be at increased risk of pulmonary toxicity. 5.5 Infusion-Related Reactions, Hypersensitivity Reactions Treatment with KADCYLA has not been studied in patients who had trastuzumab permanently discontinued due to infusion-related reactions (IRRs) and/or hypersensitivity; treatment with KADCYLA is not recommended for these patients. Infusion-related reactions, characterized by one or more of the following symptoms − flushing, chills, pyrexia, dyspnea, hypotension, wheezing, bronchospasm, and tachycardia have been reported in clinical trials of KADCYLA. In EMILIA, the overall incidence of IRRs in patients treated with KADCYLA was 1.4%. In KATHERINE, the overall incidence of IRRs in patients treated with KADCYLA was 1.6% [see Adverse Reactions (6.1) ] . In most patients, these reactions resolved over the course of several hours to a day after the infusion was terminated. KADCYLA treatment should be interrupted in patients with severe IRR. KADCYLA treatment should be permanently discontinued in the event of a life-threatening IRR [see Dosage and Administration (2.2) ] . Patients should be observed closely for IRR reactions, especially during the first infusion. One case of a serious, allergic/anaphylactic-like reaction has been observed in clinical trials of single-agent KADCYLA. Medications to treat such reactions, as well as emergency equipment, should be available for immediate use. 5.6 Hemorrhage Cases of hemorrhagic events, including central nervous system, respiratory, and gastrointestinal hemorrhage, have been reported in clinical trials with KADCYLA. Some of these bleeding events resulted in fatal outcomes. In EMILIA, the overall incidence of hemorrhage was 32% in the KADCYLA-treated group and 16% in the lapatinib plus capecitabine-treated group. The incidence of Grade ≥ 3 hemorrhage was 1.8% in the KADCYLA-treated group and 0.8% in the lapatinib plus capecitabine-treated group. In KATHERINE, the overall incidence of hemorrhage was 29% in the KADCYLA-treated group and 10% in the trastuzumab-treated group. The incidence of Grade ≥ 3 hemorrhage was 0.4% in the KADCYLA-treated group, with one fatal case of intracranial hemorrhage, and 0.3% in the trastuzumab-treated group [see Adverse Reactions (6.1) ] . Although, in some of the observed cases the patients were also receiving anti-coagulation therapy, antiplatelet therapy, or had thrombocytopenia, in others there were no known additional risk factors. Use caution with these agents and consider additional monitoring when concomitant use is medically necessary. 5.7 Thrombocytopenia Thrombocytopenia, or decreased platelet count, was reported in clinical trials of KADCYLA (145 of 1624 treated patients with Grade ≥ 3; 494 of 1624 treated patients with any Grade). The majority of these patients had Grade 1 or 2 events (< LLN to ≥ 50,000/mm 3 ) with the nadir occurring by day 8 and generally improving to Grade 0 or 1 (≥ 75,000/mm 3 ) by the next scheduled dose. In clinical trials of KADCYLA, the incidence and severity of thrombocytopenia were higher in Asian patients. In EMILIA, the overall incidence of thrombocytopenia was 31% in the KADCYLA-treated group and 3.3% in the lapatinib plus capecitabine-treated group [see Adverse Reactions (6.1) ] . The incidence of Grade ≥ 3 thrombocytopenia was 15% in the KADCYLA-treated group and 0.4% in the lapatinib plus capecitabine-treated group. In Asian patients, the incidence of Grade ≥ 3 thrombocytopenia was 45% in the KADCYLA-treated group and 1.3% in the lapatinib plus capecitabine-treated group. In KATHERINE, the overall incidence of thrombocytopenia was 29% in the KADCYLA-treated group and 2.4% in the trastuzumab-treated group [see Adverse Reactions (6.1) ] . The incidence of Grade ≥ 3 thrombocytopenia was 6% in the KADCYLA-treated group and 0.3% in the trastuzumab-treated group. In Asian patients, the incidence of Grade ≥ 3 thrombocytopenia was 19% in the KADCYLA-treated group and 0% in the trastuzumab-treated group. The overall incidence of thrombocytopenia in the KADCYLA-treated group for Asian patients was 50%. Monitor platelet counts prior to initiation of KADCYLA and prior to each KADCYLA dose [see Dosage and Administration (2.2) ] . KADCYLA has not been studied in patients with platelet counts < 100,000/mm 3 prior to initiation of treatment. In the event of decreased platelet count to Grade ≥ 3 (< 50,000/mm 3 ) do not administer KADCYLA until platelet counts recover to Grade 1 (≥ 75,000/mm 3 ) [see Dosage and Administration (2.2) ] . Closely monitor patients with thrombocytopenia (< 100,000/mm 3 ) and patients on anti-coagulant treatment during treatment with KADCYLA. 5.8 Neurotoxicity Peripheral neuropathy, mainly as Grade 1 and predominantly sensory, was reported in clinical trials of KADCYLA (26 of 1624 treated patients with Grade ≥ 3; 435 of 1624 treated patients with any Grade). In EMILIA, the overall incidence of peripheral neuropathy was 21% in the KADCYLA-treated group and 14% in the lapatinib plus capecitabine-treated group [see Adverse Reactions (6.1) ] . The incidence of Grade ≥ 3 peripheral neuropathy was 2.2% in the KADCYLA-treated group and 0.2% in the lapatinib plus capecitabine-treated group. In KATHERINE, the overall incidence of peripheral neuropathy was 32% in the KADCYLA-treated group and 17% in the trastuzumab-treated group. Peripheral neuropathy, including sensory and motor peripheral neuropathy, for KADCYLA treated patients 30% of cases were not resolved at the time of the primary IDFS analysis for KATHERINE. The incidence of Grade ≥ 3 peripheral neuropathy was 1.6% in the KADCYLA-treated group and 0.1% in the trastuzumab-treated group. KADCYLA should be temporarily discontinued in patients experiencing Grade 3 or 4 peripheral neuropathy until resolution to Grade ≤ 2. Patients should be clinically monitored on an ongoing basis for signs or symptoms of neurotoxicity [see Nonclinical Toxicology (13.2) ] . 5.9 Extravasation In KADCYLA clinical studies, reactions secondary to extravasation have been observed. These reactions, observed more frequently within 24 hours of infusion, were usually mild and comprised erythema, tenderness, skin irritation, pain, or swelling at the infusion site. Specific treatment for KADCYLA extravasation is unknown. The infusion site should be closely monitored for possible subcutaneous infiltration during drug administration."],"clinical_studies_table":["
Table 7 Summary of Efficacy from EMILIA
KADCYLA N=495Lapatinib+Capecitabine N=496
PFS: progression-free survival; OR: objective response
Progression-Free Survival (independent review)
Number (%) of patients with event265 (53.5%)304 (61.3%)
Median duration of PFS (months)9.66.4
Hazard Ratio (stratifiedStratified by world region (United States, Western Europe, other), number of prior chemotherapeutic regimens for locally advanced or metastatic disease (0-1 vs. > 1), and visceral vs. non-visceral disease.)0.650
95% CI for Hazard Ratio(0.549, 0.771)
p-value (Log-Rank test, stratified)< 0.0001
Overall Survival The second interim analysis for OS was conducted when 331 events were observed and the results are presented in this table.
Number (%) of patients who died149 (30.1%)182 (36.7%)
Median duration of survival (months)30.925.1
Hazard Ratio (stratified)0.682
95% CI for Hazard Ratio(0.548, 0.849)
p-value (Log-Rank test)0.0006
Objective Response Rate (independent review)
Patients with measurable disease397389
Number of patients with OR (%)173 (43.6%)120 (30.8%)
Difference (95% CI)12.7% (6.0, 19.4)
Duration of Objective Response (months)
Number of patients with OR173120
Median duration (95% CI)12.6 (8.4, 20.8) 6.5 (5.5, 7.2)
","
Table 8 Efficacy Results from KATHERINE
KADCYLA N=743Trastuzumab N=743
HR: Hazard Ratio; CI: Confidence Intervals,
Invasive Disease-Free Survival (IDFS)Hierarchical testing applied for IDFS and OS,Data from the pre-specified interim analysis of IDFS (67% of the number of events for the planned final analysis) with the p-value compared with the allocated alpha of 0.012
Number (%) of patients with event91 (12.2%)165 (22.2%)
HR [95% CI]Unstratified analysis0.50 [0.39, 0.64]
p-value (Log-Rank test, unstratified)< 0.0001
3-year event-free rate3-year event-free rate derived from Kaplan-Meier estimates, % [95% CI]88.3 [85.8, 90.7]77.0 [73.8, 80.7]
Overall Survival (OS),Data from the pre-specified second interim analysis of OS (82% of the number of events for the planned final analysis) with the p-value compared with the allocated alpha of 0.0263 based on the actual number of OS events at the time of the analysis
Number (%) of patients with event89 (12.0%)126 (17.0%)
HR [95% CI]0.66 [0.51, 0.87]
p-value (Log-Rank test, unstratified)0.0027
IDFS including second primary non-breast cancer
Number (%) of patients with event95 (12.8%)167 (22.5%)
HR [95% CI]0.51 [0.40, 0.66]
3-year event-free rate, % [95% CI]87.7 [85.2, 90.2]76.9 [73.7, 80.1]
Disease-Free Survival (DFS)
Number (%) of patients with event98 (13.2%)167 (22.5%)
HR [95% CI]0.53 [0.41, 0.68]
3-year event-free rate, % [95% CI]87.4 [84.9, 89.9]76.9 [73.7, 80.1]
"],"nonclinical_toxicology":["13 NONCLINICAL TOXICOLOGY 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenicity studies have not been conducted with ado-trastuzumab emtansine. DM1 was aneugenic or clastogenic in an in vivo single-dose rat bone marrow micronucleus assay at exposures that were comparable to mean maximum concentrations of DM1 measured in humans administered KADCYLA. DM1 was not mutagenic in an in vitro bacterial reverse mutation (Ames) assay. Based on results from animal toxicity studies, KADCYLA may impair fertility in humans. In a single-dose toxicity study of ado-trastuzumab emtansine in rats, degeneration of seminiferous tubules with hemorrhage in the testes associated with increased weights of testes and epididymides at a severely toxic dose level (60 mg/kg; about 4 times the clinical exposure based on AUC) were observed. The same dose in female rats resulted in signs of hemorrhage and necrosis of the corpus luteum in ovaries. In monkeys dosed with ado-trastuzumab emtansine once every three weeks for 12 weeks (four doses), at up to 30 mg/kg (about 7 times the clinical exposure based on AUC), there were decreases in the weights of epididymides, prostate, testes, seminal vesicles and uterus, although the interpretation of these effects is unclear due to the varied sexual maturity of enrolled animals. 13.2 Animal Toxicology and/or Pharmacology In monkeys, treatment with doses of ado-trastuzumab emtansine up to 30 mg/kg (about 7 times the clinical exposure based on AUC) caused dose dependent axonal degeneration in the sciatic nerve with hypertrophy or hyperplasia of the Schwann cells, and axonal degeneration of the dorsal funiculus in the spinal cord. Based on the mechanism of action of the cytotoxic component DM1, there is clinical potential for neurotoxicity [see Warnings and Precautions (5.8) ]."],"adverse_reactions_table":["
Table 3 Adverse Reactions Occurring in ≥ 10% of Patients on the KADCYLA Treatment Arm in the EMILIA TrialGrouped terms were used for the following Adverse Reactions: Thrombocytopenia: thrombocytopenia, platelet count decreased Anemia: anemia, hemoglobin decreased Abdominal pain: abdominal pain, abdominal pain upper Stomatitis: stomatitis, mucosal inflammation, oropharyngeal pain Transaminases Increased: transaminases increased, aspartate aminotransferase increased, alanine aminotransferase increased, gamma-glutamyltransferase increased, liver function test abnormal, hepatic enzyme increased, hepatic function abnormal Hypokalemia: hypokalemia, blood potassium decreased Musculoskeletal Pain: muscle spasms, musculoskeletal discomfort, musculoskeletal chest pain, back pain, pain in extremity, bone pain, musculoskeletal pain Peripheral neuropathy: neuropathy peripheral, peripheral sensory neuropathy, peripheral motor neuropathy, paresthesia Hemorrhage: Hemorrhage terms (excl laboratory terms) (SMQ, wide), Hemorrhage laboratory terms (SMQ, narrow).
Adverse ReactionsKADCYLA (3.6 mg/kg) n=490Lapatinib (1250 mg) + Capecitabine (2000 mg/m2) n=488
All Grades (%)Grade 3 – 4 (%)All Grades (%)Grade 3 – 4 (%)
SMQ=standardized MedDRA queries
Blood and Lymphatic System Disorders
Thrombocytopenia31153.30.4
Anemia144.1112.5
Gastrointestinal Disorders
Nausea400.8452.5
Constipation270.4110
Diarrhea241.68021
Vomiting190.8304.5
Abdominal pain190.8181.6
Dry Mouth1704.90.2
Stomatitis140.2332.5
General Disorders and Administration
Fatigue362.5283.5
Pyrexia190.280.4
Asthenia180.4181.6
Investigations
Transaminases increased298.0142.5
Metabolism and Nutrition Disorders
Hypokalemia102.794.7
Musculoskeletal and Connective Tissue Disorders
Musculoskeletal pain361.8311.4
Arthralgia190.680
Myalgia140.63.70
Nervous System Disorders
Headache280.8150.8
Peripheral neuropathy212.2140.2
Dizziness100.4110.2
Psychiatric Disorders
Insomnia120.490.2
Respiratory, Thoracic, and Mediastinal Disorders
Epistaxis230.280
Cough180.2130.2
Dyspnea120.880.4
Skin and Subcutaneous Tissue Disorders
Rash120281.8
Vascular Disorders
Hemorrhage321.8160.8
","
Table 4 Selected Laboratory Abnormalities (EMILIA)
ParameterKADCYLA (3.6 mg/kg)Lapatinib (1250 mg) + Capecitabine (2000 mg/m2)
All Grades (%)Grade 3 (%)Grade 4 (%)All Grades (%)Grade 3 (%)Grade 4 (%)
Chemistry
Increased AST9870.56530
Increased ALT8250.25430
Decreased potassium33303160.8
Increased bilirubin170.605720
Hematology
Decreased platelet count83143210.40.6
Decreased hemoglobin60416430.2
Decreased neutrophils3930.63862
","
Table 5 Adverse Reactions Occurring in ≥ 10% of Patients in the KATHERINE TrialGrouped terms were used for the following Adverse Reactions: Thrombocytopenia: thrombocytopenia, platelet count decreased Anemia: anemia, hemoglobin decreased Stomatitis: stomatitis, mucosal inflammation, oropharyngeal pain Abdominal pain: abdominal pain, abdominal pain upper Urinary Tract Infection: urinary tract infection, cystitis Transaminases Increased: transaminases increased, aspartate aminotransferase increased, alanine aminotransferase increased, gamma-glutamyltransferase increased, liver function test abnormal, hepatic enzyme increased, hepatic function abnormal Musculoskeletal Pain: muscle spasms, musculoskeletal discomfort, musculoskeletal chest pain, back pain, pain in extremity, bone pain, musculoskeletal pain Peripheral neuropathy: neuropathy peripheral, peripheral sensory neuropathy, peripheral motor neuropathy, paresthesia Hemorrhage: Hemorrhage terms (excl laboratory terms) (SMQ, wide), Hemorrhage laboratory terms (SMQ, narrow)
Adverse ReactionsKADCYLA n=740Trastuzumab n=720
All grades (%)Grade 3 – 4 (%)All grades (%)Grade 3 – 4 (%)
SMQ=standardized MedDRA queries
Blood and Lymphatic System Disorders
Thrombocytopenia2962.40.3
Anemia101.190.1
Gastrointestinal Disorders
Nausea420.5130.3
Constipation170.180
Stomatitis150.180.1
Vomiting150.550.3
Dry Mouth140.11.30
Diarrhea120.8130.3
Abdominal pain110.470.3
General Disorders and Administration
Fatigue501.1340.1
Pyrexia10040
Infections and Infestations
Urinary tract infection100.360.1
Investigations
Transaminases increased321.580.4
Musculoskeletal and Connective Tissue Disorders
Musculoskeletal pain300.7290.7
Arthralgia260.1210
Myalgia150.4110
Nervous System Disorders
Headache280170.1
Peripheral neuropathy281.6140.1
Dizziness100.180.3
Psychiatric Disorders
Insomnia140120.1
Respiratory, Thoracic, and Mediastinal Disorders
Epistaxis2203.50
Cough140.1120
Vascular Disorders
Hemorrhage290.4Included one fatal hemorrhage.100.3
","
Table 6 Selected Laboratory Abnormalities (KATHERINE)
ParameterKADCYLA n=740Trastuzumab n=720
All Grade (%)Grade 3 (%)Grade 4 (%)All Grade (%)Grade 3 (%)Grade 4 (%)
Chemistry
Increased AST790.80210.10
Increased ALT550.70210.10
Decreased potassium2620.590.70.1
Increased bilirubin120040.70
Hematology
Decreased platelet count5142130.10.1
Decreased hemoglobin3110290.30
Decreased neutrophils2410190.60.6
"],"information_for_patients":["17 PATIENT COUNSELING INFORMATION Hepatotoxicity Inform patients of the possibility of severe liver injury and advise patients to immediately seek medical attention if they experience symptoms of acute hepatitis such as nausea, vomiting, abdominal pain (especially RUQ abdominal pain), jaundice, dark urine, generalized pruritus, anorexia, etc. [see Warnings and Precautions (5.1) ]. Left Ventricular Dysfunction Advise patients to contact a health care professional immediately for any of the following: new onset or worsening shortness of breath, cough, swelling of the ankles/legs, palpitations, weight gain of more than 5 pounds in 24 hours, dizziness or loss of consciousness [see Warnings and Precautions (5.2) ] . Embryo-Fetal Toxicity Advise pregnant women and females of reproductive potential that KADCYLA exposure during pregnancy or within 7 months prior to conception can result in fetal harm. Advise female patients to contact their healthcare provider with a known or suspected pregnancy [see Use in Specific Populations (8.1 , 8.3) ]. Encourage women who are exposed to KADCYLA during pregnancy or who become pregnant within 7 months following the last dose of KADCYLA to report their pregnancy to Genentech [see Use in Specific Populations (8.1) ]. Advise females of reproductive potential to use effective contraception during treatment and for 7 months following the last dose of KADCYLA [see Use in Specific Populations (8.1 , 8.3) ]. Advise male patients with female partners of reproductive potential to use effective contraception during treatment and for 4 months following the last dose of KADCYLA [see Use in Specific Populations (8.3) ]. Lactation Advise women not to breastfeed during treatment and for 7 months after the last dose of KADCYLA [see Use in Specific Populations (8.2) ]."],"spl_unclassified_section":["KADCYLA ® [ado-trastuzumab emtansine] Manufactured by: Genentech, Inc . A Member of the Roche Group 1 DNA Way South San Francisco, CA 94080-4990 U.S. License No: 1048 KADCYLA is a trademark of Genentech, Inc. © 2025 Genentech, Inc. Representative sample of labeling (see the HOW SUPPLIED section for complete listing):"],"dosage_and_administration":["2 DOSAGE AND ADMINISTRATION Do not substitute KADCYLA for or with trastuzumab. HER2 Testing: Perform using FDA-authorized tests by laboratories with demonstrated proficiency. ( 2.1 ) For intravenous infusion only . Do not administer as an intravenous push or bolus. Do not use Dextrose (5%) solution. ( 2.4 ) The recommended dose of KADCYLA is 3.6 mg/kg given as an intravenous infusion every 3 weeks (21-day cycle) until disease progression or unacceptable toxicity, or a total of 14 cycles for patients with EBC. Do not administer KADCYLA at doses greater than 3.6 mg/kg. ( 2.2 ) Management of adverse reactions (infusion-related reactions, hepatotoxicity, left ventricular cardiac dysfunction, thrombocytopenia, pulmonary toxicity or peripheral neuropathy) may require temporary interruption, dose reduction, or treatment discontinuation of KADCYLA. ( 2.3 ) 2.1 Patient Selection Select patients based on HER2 protein overexpression or HER2 gene amplification in tumor specimens [see Indications and Usage (1) , Clinical Studies (14) ]. Assessment of HER2 protein overexpression and/or HER2 gene amplification should be performed using FDA-authorized tests specific for breast cancers by laboratories with demonstrated proficiency. Information on the FDA-authorized tests for the detection of HER2 protein overexpression and HER2 gene amplification is available at: http://www.fda.gov/CompanionDiagnostics. Improper assay performance, including use of sub-optimally fixed tissue, failure to utilize specified reagents, deviation from specific assay instructions, and failure to include appropriate controls for assay validation, can lead to unreliable results. 2.2 Recommended Doses and Schedules Do not substitute trastuzumab for or with KADCYLA. The recommended dose of KADCYLA is 3.6 mg/kg given as an intravenous infusion every 3 weeks (21-day cycle). Do not administer KADCYLA at doses greater than 3.6 mg/kg . Closely monitor the infusion site for possible subcutaneous infiltration during drug administration [see Warnings and Precautions (5.9) ] . First infusion: Administer infusion over 90 minutes. Observe patients during the infusion and for at least 90 minutes following the initial dose for fever, chills, or other infusion-related reactions [see Warnings and Precautions (5.5) ] . Subsequent infusions: Administer over 30 minutes if prior infusions were well tolerated. Observe patients during the infusion and for at least 30 minutes after infusion. Metastatic Breast Cancer (MBC) Patients with MBC should receive treatment until disease progression or unmanageable toxicity. Early Breast Cancer (EBC) Patients with EBC should receive treatment for a total of 14 cycles unless there is disease recurrence or unmanageable toxicity. 2.3 Dose Modifications Do not re-escalate the KADCYLA dose after a dose reduction is made. If a planned dose is delayed or missed, administer as soon as possible; do not wait until the next planned cycle. Adjust the schedule of administration to maintain a 3-week interval between doses. Administer the infusion at the dose and rate the patient tolerated in the most recent infusion. Slow or interrupt the infusion rate of KADCYLA if the patient develops an infusion-related reaction. Permanently discontinue KADCYLA for life-threatening infusion-related reactions [see Warnings and Precautions (5.5) ] . Management of increased serum transaminases, hyperbilirubinemia, left ventricular dysfunction, thrombocytopenia, pulmonary toxicity or peripheral neuropathy may require temporary interruption, dose reduction or treatment discontinuation of KADCYLA as per guidelines provided in Tables 1 and 2 . Table 1 Recommended Dose Reduction Schedule for Adverse Reactions Dose Reduction Schedule Dose Level Starting dose 3.6 mg/kg First dose reduction 3 mg/kg Second dose reduction 2.4 mg/kg Requirement for further dose reduction Discontinue treatment Table 2 Dose Modification Guidelines for KADCYLA ALT = alanine transaminase; AST = aspartate transaminase, CHF = congestive heart failure, DILI = Drug Induced Liver Injury; LVEF = left ventricular ejection fraction, LVSD = left ventricular systolic dysfunction, TBILI = Total Bilirubin, ULN = upper limit of normal Dose Modifications for Patients with MBC Adverse reaction Severity Treatment modification Increased Transaminase (AST/ALT) Grade 2 (> 2.5 to ≤ 5× the ULN) Treat at the same dose level. Grade 3 (> 5 to ≤ 20× the ULN) Do not administer KADCYLA until AST/ALT recovers to Grade ≤ 2, and then reduce one dose level Grade 4 (> 20× the ULN) Discontinue KADCYLA Hyperbilirubinemia Grade 2 (> 1.5 to ≤ 3× the ULN) Do not administer KADCYLA until total bilirubin recovers to Grade ≤ 1, and then treat at the same dose level. Grade 3 (> 3 to ≤ 10× the ULN) Do not administer KADCYLA until total bilirubin recovers to Grade ≤ 1 and then reduce one dose level. Grade 4 (> 10× the ULN) Discontinue KADCYLA Drug Induced Liver Injury (DILI) Serum transaminases > 3 × ULN and concomitant total bilirubin > 2 × ULN Permanently discontinue KADCYLA in the absence of another likely cause for the elevation of liver enzymes and bilirubin, e.g. liver metastasis or concomitant medication Nodular Regenerative Hyperplasia (NRH) All Grades Permanently discontinue KADCYLA Thrombocytopenia Grade 3 (25,000 to < 50,000/mm 3 ) Do not administer KADCYLA until platelet count recovers to Grade ≤ 1 (≥ 75,000/mm 3 ), and then treat at the same dose level Grade 4 (< 25,000/mm 3 ) Do not administer KADCYLA until platelet count recovers to Grade ≤ 1 (≥ 75,000/mm 3 ), and then reduce one dose level Left Ventricular Dysfunction Symptomatic CHF Discontinue KADCYLA LVEF < 40% Do not administer KADCYLA Repeat LVEF assessment within 3 weeks. If LVEF < 40% is confirmed, discontinue KADCYLA LVEF 40% to ≤ 45% and decrease is ≥ 10% points from baseline Do not administer KADCYLA Repeat LVEF assessment within 3 weeks. If the LVEF has not recovered to within 10% points from baseline, discontinue KADCYLA LVEF 40% to ≤ 45% and decrease is < 10% points from baseline Continue treatment with KADCYLA . Repeat LVEF assessment within 3 weeks. LVEF > 45% Continue treatment with KADCYLA . Pulmonary Toxicity Interstitial lung disease (ILD) or pneumonitis Permanently discontinue KADCYLA Peripheral Neuropathy Grade 3-4 Do not administer KADCYLA until resolution Grade ≤ 2 Dose Modification Guidelines for EBC Adverse reaction Severity Treatment modification Increased Alanine Transaminase (ALT) Grade 2-3 (> 3.0 to ≤ 20 × ULN on day of scheduled treatment) Do not administer KADCYLA until ALT recovers to Grade ≤ 1, and then reduce one dose level Grade 4 (> 20 × ULN at any time) Discontinue KADCYLA Increased Aspartate Transaminase (AST) Grade 2 (> 3.0 to ≤ 5 × ULN on day of scheduled treatment) Do not administer KADCYLA until AST recovers to Grade ≤ 1, and then treat at the same dose level Grade 3 (> 5 to ≤ 20 × ULN on day of scheduled treatment) Do not administer KADCYLA until AST recovers to Grade ≤ 1, and then reduce one dose level Grade 4 (> 20 × ULN at any time) Discontinue KADCYLA Hyperbilirubinemia TBILI > 1.0 to ≤ 2.0 × the ULN on day of scheduled treatment Do not administer KADCYLA until total bilirubin recovers to ≤ 1.0 × ULN, and then reduce one dose level TBILI > 2 × ULN at any time Discontinue KADCYLA Nodular Regenerative Hyperplasia (NRH) All Grades Permanently discontinue KADCYLA Thrombocytopenia Grade 2-3 on day of scheduled treatment (25,000 to < 75,000/mm 3 ) Do not administer KADCYLA until platelet count recovers to Grade ≤ 1 (≥ 75,000/mm 3 ), and then treat at the same dose level. If a patient requires 2 delays due to thrombocytopenia, consider reducing dose by one level. Grade 4 at any time < 25,000/mm 3 Do not administer KADCYLA until platelet count recovers to Grade ≤ 1 (≥ 75,000/mm 3 ), and then reduce one dose level. Left Ventricular Dysfunction LVEF < 45% Do not administer KADCYLA Repeat LVEF assessment within 3 weeks. If LVEF < 45% is confirmed, discontinue KADCYLA. LVEF 45% to < 50% and decrease is ≥ 10% points from baseline Prior to starting KADCYLA treatment Do not administer KADCYLA Repeat LVEF assessment within 3 weeks. If the LVEF remains < 50% and has not recovered to < 10% points from baseline, discontinue KADCYLA. LVEF 45% to < 50% and decrease is < 10% points from baseline Continue treatment with KADCYLA. Repeat LVEF assessment within 3 weeks. LVEF ≥ 50% Continue treatment with KADCYLA. Heart Failure Symptomatic CHF, Grade 3-4 LVSD or Grade 3-4 heart failure, or Grade 2 heart failure accompanied by LVEF < 45% Discontinue KADCYLA Peripheral Neuropathy Grade 3-4 Do not administer KADCYLA until resolution Grade ≤ 2 Pulmonary Toxicity Interstitial lung disease (ILD) or pneumonitis Permanently discontinue KADCYLA Radiotherapy-Related Pneumonitis Grade 2 Discontinue KADCYLA if not resolving with standard treatment Grade 3-4 Discontinue KADCYLA 2.4 Preparation for Administration In order to prevent medication errors it is important to check the vial labels to ensure that the drug being prepared and administered is KADCYLA (ado-trastuzumab emtansine) and not trastuzumab. Administration: Administer KADCYLA as an intravenous infusion only with a 0.2 or 0.22 micron in-line polyethersulfone (PES) filter. Do not administer as an intravenous push or bolus. Do not mix KADCYLA, or administer as an infusion, with other medicinal products. Reconstitution: Use aseptic technique for reconstitution and preparation of dosing solution. Appropriate procedures for the preparation of chemotherapeutic drugs should be used. Using a sterile syringe, slowly inject 5 mL of Sterile Water for Injection or 0.45% Sodium Chloride Injection into the 100 mg KADCYLA vial, or 8 mL of Sterile Water for Injection or 0.45% Sodium Chloride Injection into the 160 mg KADCYLA vial to yield a solution containing 20 mg/mL. Swirl the vial gently until completely dissolved. Do not shake. Inspect the reconstituted solution for particulates and discoloration. The reconstituted solution should be clear to slightly opalescent and free of visible particulates. The color of the reconstituted solution should be colorless to pale brown. Do not use if the reconstituted solution contains visible particulates or is cloudy or discolored. The reconstituted lyophilized vials should be used immediately following reconstitution with Sterile Water for Injection or 0.45% Sodium Chloride Injection. If not used immediately, the reconstituted KADCYLA vials can be stored for up to 120 hours (5 days) in a refrigerator at 2°C to 8°C (36°F to 46°F); discard unused KADCYLA after 120 hours (5 days) if stored at 2°C to 8°C (36°F to 46°F). Do not freeze. The reconstituted product contains no preservative and is intended for single-dose only. Dilution: Determine the correct dose (mg) of KADCYLA [see Dosage and Administration (2.1) ] . Calculate the volume of the 20 mg/mL reconstituted KADCYLA solution needed. Withdraw this amount from the vial and add it to an infusion bag containing 250 mL of 0.9% Sodium Chloride Injection. Do not use Dextrose (5%) solution. Gently invert the bag to mix the solution in order to avoid foaming. The diluted KADCYLA infusion solution should be used immediately. If not used immediately, the solution may be stored in a refrigerator at 2°C to 8°C (36°F to 46°F) for up to 24 hours prior to use. This storage time is additional to the time allowed for the reconstituted vials. Do not freeze or shake."],"spl_product_data_elements":["KADCYLA ADO-TRASTUZUMAB EMTANSINE TRASTUZUMAB EMTANSINE TRASTUZUMAB EMTANSINE SUCROSE SUCCINIC ACID SODIUM HYDROXIDE POLYSORBATE 20 WATER KADCYLA ADO-TRASTUZUMAB EMTANSINE TRASTUZUMAB EMTANSINE TRASTUZUMAB EMTANSINE SUCROSE SUCCINIC ACID SODIUM HYDROXIDE POLYSORBATE 20 WATER"],"dosage_forms_and_strengths":["3 DOSAGE FORMS AND STRENGTHS Lyophilized powder in single-dose vials: 100 mg per vial or 160 mg per vial of ado-trastuzumab emtansine. Lyophilized powder in single-dose vials containing 100 mg per vial or 160 mg per vial. ( 3 )"],"recent_major_changes_table":["
Dosage and Administration (2.4)03/2026
"],"storage_and_handling_table":["
Carton ContentsNDC
One 100 mg vial, single-dose vialNDC 50242-088-01
One 160 mg vial, single-dose vialNDC 50242-087-01
"],"use_in_specific_populations":["8 USE IN SPECIFIC POPULATIONS Lactation: Advise not to breastfeed. ( 8.2 ) Females and Males of Reproductive Potential: Verify pregnancy status of females prior to initiation of KADCYLA. ( 8.3 ) 8.1 Pregnancy If KADCYLA is administered during pregnancy, or if a patient becomes pregnant while receiving KADCYLA or within 7 months following the last dose of KADCYLA, health care providers and patients should immediately report KADCYLA exposure to Genentech at 1-888-835-2555. Risk Summary KADCYLA can cause fetal harm when administered to a pregnant woman. There are no available data on the use of KADCYLA in pregnant women. Cases of oligohydramnios and oligohydramnios sequence manifesting as pulmonary hypoplasia, skeletal abnormalities, and neonatal death were observed in the postmarketing setting in patients treated with trastuzumab, the antibody component of KADCYLA [see Data ] . Based on its mechanism of action, the DM1 component of KADCYLA can also cause embryo-fetal harm when administered to a pregnant woman [ see Data ]. Apprise the patient of the potential risks to a fetus. There are clinical considerations if KADCYLA is used in a pregnant woman, or if a patient becomes pregnant within 7 months following the last dose of KADCYLA [see Clinical Considerations ]. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. Clinical Considerations Fetal/Neonatal Adverse Reactions Monitor women who received KADCYLA during pregnancy or within 7 months prior to conception for oligohydramnios. If oligohydramnios occurs, perform fetal testing that is appropriate for gestational age and consistent with community standards of care. Data Human Data There are no available data on the use of KADCYLA in pregnant women. In the post-marketing setting, cases of oligohydramnios, and of oligohydramnios sequence, manifesting in the fetus as pulmonary hypoplasia, skeletal abnormalities and neonatal death were observed after treatment with trastuzumab during pregnancy. These case reports described oligohydramnios in pregnant women who received trastuzumab either alone or in combination with chemotherapy. In some case reports, amniotic fluid index increased after trastuzumab was stopped. In one case, trastuzumab therapy resumed after amniotic index improved, and oligohydramnios recurred. Animal Data There were no reproductive and developmental toxicology studies conducted with ado-trastuzumab emtansine. DM1, the cytotoxic component of KADCYLA, disrupts microtubule function. DM1 is toxic to rapidly dividing cells in animals and is genotoxic, suggesting it has the potential to cause embryotoxicity and teratogenicity. In studies where trastuzumab was administered to pregnant cynomolgus monkeys during the period of organogenesis at doses up to 25 mg/kg given twice weekly (about 7 times the clinical dose), trastuzumab crossed the placental barrier during the early (Gestation Days 20 to 50) and late (Gestation Days 120 to 150) phases of gestation. The resulting concentrations of trastuzumab in fetal serum and amniotic fluid were approximately 33% and 25%, respectively, of those present in the maternal serum but were not associated with adverse developmental effects. 8.2 Lactation Risk Summary There is no information regarding the presence of ado-trastuzumab emtansine in human milk, the effects on the breastfed infant, or the effects on milk production. DM1, the cytotoxic component of KADCYLA, may cause serious adverse reactions in breastfed infants based on its mechanism of action [see Data ] . Advise women not to breastfeed during treatment and for 7 months following the last dose of KADCYLA. Data There were no animal lactation studies conducted with ado-trastuzumab emtansine or the cytotoxic component of KADCYLA (DM1). In lactating cynomolgus monkeys, trastuzumab was present in breast milk at about 0.3% of maternal serum concentrations after pre- (beginning Gestation Day 120) and post-partum (through Post-partum Day 28) doses of 25 mg/kg administered twice weekly (about 7 times the clinical dose of KADCYLA). Infant monkeys with detectable serum levels of trastuzumab did not exhibit any adverse effects on growth or development from birth to 1 month of age. 8.3 Females and Males of Reproductive Potential Pregnancy Testing Verify the pregnancy status of females of reproductive potential prior to the initiation of KADCYLA. Contraception Females KADCYLA can cause embryo-fetal harm when administered during pregnancy. Advise females of reproductive potential to use effective contraception during treatment and for 7 months following the last dose of KADCYLA [ see Use in Specific Populations (8.1) ]. Males Because of the potential for genotoxicity, advise male patients with female partners of reproductive potential to use effective contraception during treatment with KADCYLA and for 4 months following the last dose. Infertility Based on results from animal toxicity studies, KADCYLA may impair fertility in females and males of reproductive potential. It is not known if the effects are reversible [see Nonclinical Toxicology (13.1) ]. 8.4 Pediatric Use Safety and effectiveness of KADCYLA have not been established in pediatric patients. 8.5 Geriatric Use Of the 495 patients who were randomized to KADCYLA in EMILIA [see Clinical Studies (14.1) ] , 65 patients (13%) were ≥ 65 years of age and 11 patients (2%) were ≥ 75 years of age. In patients ≥ 65 years old (n=138 across both treatment arms) the hazard ratios for progression-free survival (PFS) and overall survival (OS) were 1.06 (95% CI: 0.68, 1.66) and 1.05 (95% CI: 0.58, 1.91), respectively. No overall differences in the safety of KADCYLA were observed in patients aged ≥ 65 compared to patients < 65 years of age. EMILIA did not include sufficient numbers of patients aged ≥ 75 years to draw conclusions on the safety or effectiveness of KADCYLA in this age group. Of the 743 patients who were randomized to KADCYLA in KATHERINE [see Clinical Studies (14.2) ] , 58 patients (8%) were ≥ 65 years of age and 2 patients (0.3%) were ≥ 75 years of age. No overall differences in the safety or effectiveness of KADCYLA were observed in patients aged ≥ 65 compared to patients < 65 years of age. KATHERINE did not include sufficient numbers of patients aged ≥ 75 years to draw conclusions on the safety or effectiveness of KADCYLA in this age group. Population pharmacokinetic analysis indicates that age does not have a clinically meaningful effect on the pharmacokinetics of ado-trastuzumab emtansine [see Clinical Pharmacology (12.3) ] . 8.6 Renal Impairment No dedicated renal impairment trial for KADCYLA has been conducted. Based on the population pharmacokinetics, as well as analysis of Grade 3 or greater adverse reactions and dose modifications, dose adjustments of KADCYLA are not needed in patients with mild (creatinine clearance [CLcr] 60 to 89 mL/min) or moderate (CLcr 30 to 59 mL/min) renal impairment. No dose adjustment can be recommended for patients with severe renal impairment (CLcr less than 30 mL/min) because of the limited data available [see Clinical Pharmacology (12.3) ] . 8.7 Hepatic Impairment No adjustment to the starting dose is required for patients with mild or moderate hepatic impairment [see Clinical Pharmacology (12.3) ] . KADCYLA was not studied in patients with severe hepatic impairment. Closely monitor patients with hepatic impairment due to known hepatotoxicity observed with KADCYLA [ see Warnings and Precautions, Hepatotoxicity (5.1) ]."],"dosage_and_administration_table":["
Table 1 Recommended Dose Reduction Schedule for Adverse Reactions
Dose Reduction ScheduleDose Level
Starting dose3.6 mg/kg
First dose reduction3 mg/kg
Second dose reduction2.4 mg/kg
Requirement for further dose reductionDiscontinue treatment
","
Table 2 Dose Modification Guidelines for KADCYLA
ALT = alanine transaminase; AST = aspartate transaminase, CHF = congestive heart failure, DILI = Drug Induced Liver Injury; LVEF = left ventricular ejection fraction, LVSD = left ventricular systolic dysfunction, TBILI = Total Bilirubin, ULN = upper limit of normal
Dose Modifications for Patients with MBC
Adverse reactionSeverityTreatment modification
Increased Transaminase (AST/ALT)Grade 2 (> 2.5 to ≤ 5× the ULN)Treat at the same dose level.
Grade 3 (> 5 to ≤ 20× the ULN)Do not administer KADCYLA until AST/ALT recovers to Grade ≤ 2, and then reduce one dose level
Grade 4 (> 20× the ULN)Discontinue KADCYLA
HyperbilirubinemiaGrade 2 (> 1.5 to ≤ 3× the ULN)Do not administer KADCYLA until total bilirubin recovers to Grade ≤ 1, and then treat at the same dose level.
Grade 3 (> 3 to ≤ 10× the ULN)Do not administer KADCYLA until total bilirubin recovers to Grade ≤ 1 and then reduce one dose level.
Grade 4 (> 10× the ULN)Discontinue KADCYLA
Drug Induced Liver Injury (DILI)Serum transaminases > 3 × ULN and concomitant total bilirubin > 2 × ULNPermanently discontinue KADCYLA in the absence of another likely cause for the elevation of liver enzymes and bilirubin, e.g. liver metastasis or concomitant medication
Nodular Regenerative Hyperplasia (NRH)All GradesPermanently discontinue KADCYLA
ThrombocytopeniaGrade 3 (25,000 to < 50,000/mm3)Do not administer KADCYLA until platelet count recovers to Grade ≤ 1 (≥ 75,000/mm3), and then treat at the same dose level
Grade 4 (< 25,000/mm3)Do not administer KADCYLA until platelet count recovers to Grade ≤ 1 (≥ 75,000/mm3), and then reduce one dose level
Left Ventricular DysfunctionSymptomatic CHFDiscontinue KADCYLA
LVEF < 40%Do not administer KADCYLA Repeat LVEF assessment within 3 weeks. If LVEF < 40% is confirmed, discontinue KADCYLA
LVEF 40% to ≤ 45% and decrease is ≥ 10% points from baselineDo not administer KADCYLA Repeat LVEF assessment within 3 weeks. If the LVEF has not recovered to within 10% points from baseline, discontinue KADCYLA
LVEF 40% to ≤ 45% and decrease is < 10% points from baselineContinue treatment with KADCYLA. Repeat LVEF assessment within 3 weeks.
LVEF > 45%Continue treatment with KADCYLA.
Pulmonary ToxicityInterstitial lung disease (ILD) or pneumonitisPermanently discontinue KADCYLA
Peripheral NeuropathyGrade 3-4Do not administer KADCYLA until resolution Grade ≤ 2
Dose Modification Guidelines for EBC
Adverse reactionSeverityTreatment modification
Increased Alanine Transaminase (ALT)Grade 2-3 (> 3.0 to ≤ 20 × ULN on day of scheduled treatment)Do not administer KADCYLA until ALT recovers to Grade ≤ 1, and then reduce one dose level
Grade 4 (> 20 × ULN at any time)Discontinue KADCYLA
Increased Aspartate Transaminase (AST)Grade 2 (> 3.0 to ≤ 5 × ULN on day of scheduled treatment)Do not administer KADCYLA until AST recovers to Grade ≤ 1, and then treat at the same dose level
Grade 3 (> 5 to ≤ 20 × ULN on day of scheduled treatment)Do not administer KADCYLA until AST recovers to Grade ≤ 1, and then reduce one dose level
Grade 4 (> 20 × ULN at any time)Discontinue KADCYLA
HyperbilirubinemiaTBILI > 1.0 to ≤ 2.0 × the ULN on day of scheduled treatmentDo not administer KADCYLA until total bilirubin recovers to ≤ 1.0 × ULN, and then reduce one dose level
TBILI > 2 × ULN at any timeDiscontinue KADCYLA
Nodular Regenerative Hyperplasia (NRH)All GradesPermanently discontinue KADCYLA
ThrombocytopeniaGrade 2-3 on day of scheduled treatment (25,000 to < 75,000/mm3)Do not administer KADCYLA until platelet count recovers to Grade ≤ 1 (≥ 75,000/mm3), and then treat at the same dose level. If a patient requires 2 delays due to thrombocytopenia, consider reducing dose by one level.
Grade 4 at any time < 25,000/mm3Do not administer KADCYLA until platelet count recovers to Grade ≤ 1 (≥ 75,000/mm3), and then reduce one dose level.
Left Ventricular DysfunctionLVEF < 45%Do not administer KADCYLA Repeat LVEF assessment within 3 weeks. If LVEF < 45% is confirmed, discontinue KADCYLA.
LVEF 45% to < 50% and decrease is ≥ 10% points from baselinePrior to starting KADCYLA treatmentDo not administer KADCYLA Repeat LVEF assessment within 3 weeks. If the LVEF remains < 50% and has not recovered to < 10% points from baseline, discontinue KADCYLA.
LVEF 45% to < 50% and decrease is < 10% points from baselineContinue treatment with KADCYLA. Repeat LVEF assessment within 3 weeks.
LVEF ≥ 50%Continue treatment with KADCYLA.
Heart FailureSymptomatic CHF, Grade 3-4 LVSD or Grade 3-4 heart failure, or Grade 2 heart failure accompanied by LVEF < 45%Discontinue KADCYLA
Peripheral NeuropathyGrade 3-4Do not administer KADCYLA until resolution Grade ≤ 2
Pulmonary ToxicityInterstitial lung disease (ILD) or pneumonitisPermanently discontinue KADCYLA
Radiotherapy-Related PneumonitisGrade 2Discontinue KADCYLA if not resolving with standard treatment
Grade 3-4Discontinue KADCYLA
"],"animal_pharmacology_and_or_toxicology":["13.2 Animal Toxicology and/or Pharmacology In monkeys, treatment with doses of ado-trastuzumab emtansine up to 30 mg/kg (about 7 times the clinical exposure based on AUC) caused dose dependent axonal degeneration in the sciatic nerve with hypertrophy or hyperplasia of the Schwann cells, and axonal degeneration of the dorsal funiculus in the spinal cord. Based on the mechanism of action of the cytotoxic component DM1, there is clinical potential for neurotoxicity [see Warnings and Precautions (5.8) ]."],"package_label_principal_display_panel":["PRINCIPAL DISPLAY PANEL - 100 mg Vial Carton NDC 50242-088-01 Kadcyla ® (ado-trastuzumab emtansine) For Injection 100 mg per vial For Intravenous Infusion Only Reconstitute and Dilute prior to administration Single-Dose Vial – Discard Unused Portion KEEP REFRIGERATED Rx only 1 vial Genentech 10217212 PRINCIPAL DISPLAY PANEL - 100 mg Vial Carton","PRINCIPAL DISPLAY PANEL - 160 mg Vial Carton NDC 50242-087-01 Kadcyla ® (ado-trastuzumab emtansine) For Injection 160 mg per vial For Intravenous Infusion Only Reconstitute and Dilute prior to administration Single-Dose Vial – Discard Unused Portion KEEP REFRIGERATED Rx only 1 vial Genentech 10217217 PRINCIPAL DISPLAY PANEL - 160 mg Vial Carton"],"carcinogenesis_and_mutagenesis_and_impairment_of_fertility":["13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenicity studies have not been conducted with ado-trastuzumab emtansine. DM1 was aneugenic or clastogenic in an in vivo single-dose rat bone marrow micronucleus assay at exposures that were comparable to mean maximum concentrations of DM1 measured in humans administered KADCYLA. DM1 was not mutagenic in an in vitro bacterial reverse mutation (Ames) assay. Based on results from animal toxicity studies, KADCYLA may impair fertility in humans. In a single-dose toxicity study of ado-trastuzumab emtansine in rats, degeneration of seminiferous tubules with hemorrhage in the testes associated with increased weights of testes and epididymides at a severely toxic dose level (60 mg/kg; about 4 times the clinical exposure based on AUC) were observed. The same dose in female rats resulted in signs of hemorrhage and necrosis of the corpus luteum in ovaries. In monkeys dosed with ado-trastuzumab emtansine once every three weeks for 12 weeks (four doses), at up to 30 mg/kg (about 7 times the clinical exposure based on AUC), there were decreases in the weights of epididymides, prostate, testes, seminal vesicles and uterus, although the interpretation of these effects is unclear due to the varied sexual maturity of enrolled animals."]},"tags":[{"label":"HER2/neu Receptor Antagonist","category":"class"},{"label":"Monoclonal Antibody","category":"modality"},{"label":"Receptor tyrosine-protein kinase erbB-2","category":"target"},{"label":"L01FD01","category":"atc"},{"label":"Intravenous, Subcutaneous","category":"route"},{"label":"HER2-positive carcinoma of breast","category":"indication"},{"label":"HER2-positive colon cancer","category":"indication"},{"label":"HER2-positive rectal cancer","category":"indication"},{"label":"HER2-positive salivary gland tumors","category":"indication"},{"label":"Human epidermal growth factor 2 positive gastric cancer","category":"indication"},{"label":"Secondary malignant neoplasm of female breast","category":"indication"},{"label":"Genentech","category":"company"},{"label":"Antineoplastic Agents","category":"pharmacology"},{"label":"Antineoplastic Agents, Immunological","category":"pharmacology"}],"phase":"marketed","fdaNDC":[{"route":["INTRAVENOUS"],"labeler":"Daiichi Sankyo Inc.","brandName":"Enhertu","packaging":[{"ndc":"65597-406-01","description":"1 VIAL, SINGLE-DOSE in 1 CARTON (65597-406-01) / 5 mL in 1 VIAL, SINGLE-DOSE","marketingStartDate":"20191220"}],"dosageForm":"INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION","genericName":"fam-trastuzumab deruxtecan-nxki","productType":"HUMAN PRESCRIPTION DRUG","activeIngredients":[{"name":"TRASTUZUMAB DERUXTECAN","strength":"100 mg/5mL"}],"marketingCategory":"BLA"},{"route":[],"labeler":"Boehringer Ingelheim Pharma GmbH and Co. 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FAERS","actionTaken":"1,160 reports"},{"date":"","signal":"BACK PAIN","source":"FDA FAERS","actionTaken":"1,126 reports"},{"date":"","signal":"PAIN IN EXTREMITY","source":"FDA FAERS","actionTaken":"1,108 reports"}],"drugInteractions":[{"drug":"Strong CYP3A4 inhibitors (ketoconazole, itraconazole, clarithromycin, atazanavir, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, voriconazole)","severity":"High","mechanism":"DM1 is metabolized by CYP3A4; inhibition increases DM1 exposure","management":"Avoid concomitant use. Consider alternate medication with no or minimal CYP3A4 inhibition. If unavoidable, delay KADCYLA until inhibitor clears (approximately 3 elimination half-lives). If coadministered, closely monitor for adverse reactions.","clinicalEffect":"Increased DM1 exposure and toxicity"}],"commonSideEffects":[{"effect":"DIARRHOEA","drugRate":"53.4%","placeboRate":"","totalAtRisk":6427,"totalAffected":3435,"trialsReporting":3},{"effect":"NAUSEA","drugRate":"41.7%","placeboRate":"","totalAtRisk":6427,"totalAffected":2683,"trialsReporting":3},{"effect":"Diarrhoea","drugRate":"55.4%","placeboRate":"","totalAtRisk":4198,"totalAffected":2326,"trialsReporting":3},{"effect":"FATIGUE","drugRate":"34.7%","placeboRate":"","totalAtRisk":6427,"totalAffected":2227,"trialsReporting":3},{"effect":"Fatigue","drugRate":"28.0%","placeboRate":"","totalAtRisk":6811,"totalAffected":1910,"trialsReporting":5},{"effect":"Nausea","drugRate":"32.4%","placeboRate":"","totalAtRisk":5813,"totalAffected":1883,"trialsReporting":4},{"effect":"ALOPECIA","drugRate":"38.5%","placeboRate":"","totalAtRisk":4425,"totalAffected":1703,"trialsReporting":2},{"effect":"Alopecia","drugRate":"32.3%","placeboRate":"","totalAtRisk":4405,"totalAffected":1425,"trialsReporting":3},{"effect":"RASH","drugRate":"31.4%","placeboRate":"","totalAtRisk":4425,"totalAffected":1389,"trialsReporting":2},{"effect":"ARTHRALGIA","drugRate":"21.3%","placeboRate":"","totalAtRisk":6427,"totalAffected":1370,"trialsReporting":3},{"effect":"VOMITING","drugRate":"20.5%","placeboRate":"","totalAtRisk":6427,"totalAffected":1316,"trialsReporting":3},{"effect":"ASTHENIA","drugRate":"18.8%","placeboRate":"","totalAtRisk":6427,"totalAffected":1208,"trialsReporting":3},{"effect":"CONSTIPATION","drugRate":"18.8%","placeboRate":"","totalAtRisk":6427,"totalAffected":1206,"trialsReporting":3},{"effect":"HEADACHE","drugRate":"18.4%","placeboRate":"","totalAtRisk":6427,"totalAffected":1185,"trialsReporting":3},{"effect":"EPISTAXIS","drugRate":"18.0%","placeboRate":"","totalAtRisk":6427,"totalAffected":1154,"trialsReporting":3},{"effect":"DECREASED 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PERIPHERAL","drugRate":"12.4%","placeboRate":"","totalAtRisk":4425,"totalAffected":549,"trialsReporting":2},{"effect":"BACK PAIN","drugRate":"8.4%","placeboRate":"","totalAtRisk":6427,"totalAffected":540,"trialsReporting":3},{"effect":"PARAESTHESIA","drugRate":"8.3%","placeboRate":"","totalAtRisk":6427,"totalAffected":532,"trialsReporting":3},{"effect":"PAIN IN EXTREMITY","drugRate":"8.1%","placeboRate":"","totalAtRisk":6427,"totalAffected":520,"trialsReporting":3},{"effect":"ABDOMINAL PAIN UPPER","drugRate":"8.0%","placeboRate":"","totalAtRisk":6427,"totalAffected":516,"trialsReporting":3},{"effect":"Abdominal pain","drugRate":"12.1%","placeboRate":"","totalAtRisk":4198,"totalAffected":509,"trialsReporting":3},{"effect":"DYSPEPSIA","drugRate":"11.3%","placeboRate":"","totalAtRisk":4425,"totalAffected":502,"trialsReporting":2},{"effect":"DIZZINESS","drugRate":"7.7%","placeboRate":"","totalAtRisk":6427,"totalAffected":493,"trialsReporting":3},{"effect":"Cough","drugRate":"8.4%","placeboRate":"","totalAtRisk":5813,"totalAffected":487,"trialsReporting":4},{"effect":"Stomatitis","drugRate":"11.4%","placeboRate":"","totalAtRisk":4198,"totalAffected":477,"trialsReporting":3}],"specialPopulations":{"Geriatric":"8.5 Geriatric Use Of the 495 patients who were randomized to KADCYLA in EMILIA [see Clinical Studies (14.1) ] , 65 patients (13%) were ≥ 65 years of age and 11 patients (2%) were ≥ 75 years of age. In patients ≥ 65 years old (n=138 across both treatment arms) the hazard ratios for progression-free survival (PFS) and overall survival (OS) were 1.06 (95% CI: 0.68, 1.66) and 1.05 (95% CI: 0.58, 1.91), respectively. No overall differences in the safety of KADCYLA were observed in patients aged ≥ 65 ","Pediatric":"8.4 Pediatric Use Safety and effectiveness of KADCYLA have not been established in pediatric patients.","Pregnancy":"8.1 Pregnancy If KADCYLA is administered during pregnancy, or if a patient becomes pregnant while receiving KADCYLA or within 7 months following the last dose of KADCYLA, health care providers and patients should immediately report KADCYLA exposure to Genentech at 1-888-835-2555. Risk Summary KADCYLA can cause fetal harm when administered to a pregnant woman. There are no available data on the use of KADCYLA in pregnant women. Cases of oligohydramnios and oligohydramnios sequence manifesting as ","Specific Populations":"8 USE IN SPECIFIC POPULATIONS Lactation: Advise not to breastfeed. ( 8.2 ) Females and Males of Reproductive Potential: Verify pregnancy status of females prior to initiation of KADCYLA. ( 8.3 ) 8.1 Pregnancy If KADCYLA is administered during pregnancy, or if a patient becomes pregnant while receiving KADCYLA or within 7 months following the last dose of KADCYLA, health care providers and patients should immediately report KADCYLA exposure to Genentech at 1-888-835-2555. Risk Summary KADCYLA can"},"seriousAdverseEvents":[]},"trials":[],"aliases":[],"company":"Roche","patents":[],"pricing":[],"_sources":{"fdaNDC":{"url":"","method":"api_direct","source":"FDA NDC Directory","rawText":"","confidence":1,"sourceType":"fda_ndc","retrievedAt":"2026-04-19T21:07:22.849328+00:00"},"patents":{"url":"","method":"deterministic","source":"FDA Orange Book + Purple Book","rawText":"","confidence":1,"sourceType":"fda_orange_book","retrievedAt":"2026-04-19T21:07:36.976503+00:00"},"dailyMed":{"url":"","method":"api_direct","source":"DailyMed (NIH/NLM)","rawText":"","confidence":1,"sourceType":"dailymed","retrievedAt":"2026-04-19T21:07:23.576495+00:00"},"aiSummary":{"url":"","method":"ai_extraction","source":"Haiku strategic summary","rawText":"","confidence":0.9,"sourceType":"ai_extraction","retrievedAt":"2026-04-20T07:55:09.916211+00:00"},"mechanism":{"url":"","method":"ai_extraction","source":"FDA Label + Haiku","rawText":"","confidence":0.95,"sourceType":"fda_label","retrievedAt":"2026-04-20T08:27:35.029070+00:00"},"chemblData":{"url":"https://www.ebi.ac.uk/chembl/compound_report_card/CHEMBL1201585/","method":"api_direct","source":"ChEMBL (EMBL-EBI)","rawText":"","confidence":1,"sourceType":"chembl","retrievedAt":"2026-04-19T21:07:30.098725+00:00"},"overdosage":{"url":"","method":"deterministic","source":"FDA Label (overdosage)","rawText":"","confidence":1,"sourceType":"fda_label","retrievedAt":"2026-04-19T21:04:58.506394+00:00"},"howSupplied":{"url":"","method":"deterministic","source":"FDA Label (how_supplied)","rawText":"16 HOW SUPPLIED/STORAGE AND HANDLING 16.1 How Supplied/Storage KADCYLA (ado-trastuzumab emtansine) is supplied as: Carton Contents NDC One 100 mg vial, single-dose vial NDC 50242-088-01 One 160 mg vial, single-dose vial NDC 50242-087-01 Store vials in a refrigerator at 2°C to 8°C (36°F to 46°F) until time of reconstitution. Do not freeze or shake. 16.2 Special Handling Follow procedures for proper handling and disposal of anticancer drugs.","confidence":1,"sourceType":"fda_label","retrievedAt":"2026-04-19T21:04:38.011516+00:00"},"trialDetails":{"url":"","method":"deterministic","source":"ClinicalTrials.gov (0 trials with endpoints)","rawText":"","confidence":1,"sourceType":"ctgov_results","retrievedAt":"2026-04-19T21:07:49.371149+00:00"},"targetProtein":{"url":"https://www.uniprot.org/uniprot/A0A8A0Y2Q6","method":"api_direct","source":"UniProt (EMBL-EBI)","rawText":"","confidence":1,"sourceType":"uniprot","retrievedAt":"2026-04-19T21:07:23.909058+00:00"},"drugDescription":{"url":"","method":"ai_extraction","source":"FDA Label (description)","aiModel":"featherless","rawText":"11 DESCRIPTION KADCYLA (ado-trastuzumab emtansine) is a HER2-targeted antibody-drug conjugate (ADC) which contains the humanized anti-HER2 IgG1, trastuzumab, covalently linked to the microtubule inhibitory drug DM1 (a maytansine derivative) via the stable thioether linker MCC (4-[N-maleimidomethyl] cyclohexane-1-carboxylate). Emtansine refers to the MCC-DM1 complex. The antibody trastuzumab, is a well characterized recombinant monoclonal antibody product produced by mammalian (Chinese hamster ov","confidence":0.95,"sourceType":"fda_label","retrievedAt":"2026-04-19T21:04:58.506319+00:00"},"pharmacokinetics":{"url":"","method":"ai_extraction","source":"FDA Label + Haiku","rawText":"","confidence":0.95,"sourceType":"fda_label","retrievedAt":"2026-04-20T08:27:35.029094+00:00"},"publicationCount":{"url":"","method":"api_direct","source":"PubMed/NCBI","rawText":"","confidence":1,"sourceType":"pubmed","retrievedAt":"2026-04-19T21:07:28.754034+00:00"},"faersTotalReports":{"url":"","method":"api_direct","source":"FDA FAERS","rawText":"","confidence":1,"sourceType":"fda_faers","retrievedAt":"2026-04-19T21:07:28.210773+00:00"},"fdaClinicalStudies":{"url":"","method":"ai_extraction","source":"FDA Label (clinical_studies, 12,573 chars)","aiModel":"featherless","rawText":"14 CLINICAL STUDIES 14.1 Metastatic Breast Cancer The efficacy of KADCYLA was evaluated in a randomized, multicenter, open-label trial (EMILIA) (NCT00829166) of 991 patients with HER2-positive, unresectable locally advanced or metastatic breast cancer. Prior taxane and trastuzumab-based therapy was required before trial enrollment. Patients with only prior adjuvant therapy were required to have disease recurrence during or within six months of completing adjuvant therapy. Breast tumor samples we","confidence":0.9,"sourceType":"fda_label","retrievedAt":"2026-04-19T21:05:27.773574+00:00"},"recentPublications":{"url":"","method":"api_direct","source":"PubMed/NCBI","rawText":"","confidence":1,"sourceType":"pubmed","retrievedAt":"2026-04-19T21:07:29.703567+00:00"},"rxnormFormulations":{"url":"https://rxnav.nlm.nih.gov/REST/drugs.json?name=trastuzumab","method":"api_direct","source":"RxNorm (NIH)","rawText":"","confidence":1,"sourceType":"rxnorm","retrievedAt":"2026-04-19T21:07:22.450563+00:00"},"participantFlowData":{"url":"","method":"deterministic","source":"ClinicalTrials.gov participantFlowModule","rawText":"","confidence":1,"sourceType":"ctgov_results","retrievedAt":"2026-04-19T21:07:49.371038+00:00"},"companionDiagnostics":{"url":"","method":"ai_extraction","source":"FDA Label + Haiku","rawText":"","confidence":0.95,"sourceType":"fda_label","retrievedAt":"2026-04-20T07:55:09.916207+00:00"},"safety.safetySignals":{"url":"","method":"api_direct","source":"FDA FAERS","rawText":"","confidence":1,"sourceType":"fda_faers","retrievedAt":"2026-04-19T21:07:24.356666+00:00"},"mechanism.oneSentence":{"url":"","method":"ai_extraction","source":"FDA Label + Haiku extraction","aiModel":"claude-haiku-4-5","rawText":"","confidence":0.95,"sourceType":"fda_label","retrievedAt":"2026-04-20T07:55:09.916163+00:00"},"nonclinicalToxicology":{"url":"","method":"deterministic","source":"FDA Label (nonclinical_toxicology)","rawText":"13 NONCLINICAL TOXICOLOGY 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenicity studies have not been conducted with ado-trastuzumab emtansine. DM1 was aneugenic or clastogenic in an in vivo single-dose rat bone marrow micronucleus assay at exposures that were comparable to mean maximum concentrations of DM1 measured in humans administered KADCYLA. DM1 was not mutagenic in an in vitro bacterial reverse mutation (Ames) assay. Based on results from animal toxicity studies, KADC","confidence":1,"sourceType":"fda_label","retrievedAt":"2026-04-19T21:04:58.506390+00:00"},"structuredTrialResults":{"url":"","method":"deterministic","source":"ClinicalTrials.gov resultsSection (0 trials)","rawText":"","confidence":1,"sourceType":"ctgov_results","retrievedAt":"2026-04-19T21:07:49.371034+00:00"},"safety.drugInteractions":{"url":"","method":"ai_extraction","source":"FDA Label + Haiku","rawText":"","confidence":0.95,"sourceType":"fda_label","retrievedAt":"2026-04-20T07:55:09.916198+00:00"},"commercial.annualRevenue":{"url":"","method":"deterministic","source":"SEC EDGAR 10-K","rawText":"$2900M FY2024","confidence":1,"sourceType":"sec_edgar","retrievedAt":"2026-04-19T21:07:36.976571+00:00"},"safety.commonSideEffects":{"url":"","method":"deterministic","source":"ClinicalTrials.gov (0 trials with results)","rawText":"","confidence":1,"sourceType":"ctgov_results","retrievedAt":"2026-04-19T21:07:49.370961+00:00"},"safety.specialPopulations":{"url":"","method":"deterministic","source":"FDA Label (special populations)","rawText":"","confidence":1,"sourceType":"fda_label","retrievedAt":"2026-04-19T21:07:04.344636+00:00"},"safety.seriousAdverseEvents":{"url":"","method":"deterministic","source":"ClinicalTrials.gov (0 trials)","rawText":"","confidence":1,"sourceType":"ctgov_results","retrievedAt":"2026-04-19T21:07:49.370997+00:00"}},"allNames":"herceptin, herzuma, kanjinti, ogivri, ontruzant, trazimera","dailyMed":[{"url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=b9c5e894-27d2-4245-a653-df986fed3c56","setid":"b9c5e894-27d2-4245-a653-df986fed3c56","title":"TRAZIMERA (TRASTUZUMAB-QYYP) KIT TRAZIMERA (TRASTUZUMAB-QYYP) INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION [PFIZER LABORATORIES DIV PFIZER INC]"},{"url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=23f3c1f4-0fc8-4804-a9e3-04cf25dd302e","setid":"23f3c1f4-0fc8-4804-a9e3-04cf25dd302e","title":"KADCYLA (ADO-TRASTUZUMAB EMTANSINE) INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION [GENENTECH, INC.]"},{"url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=9a94f5b2-b84e-4987-8ea1-c4346db5a5fa","setid":"9a94f5b2-b84e-4987-8ea1-c4346db5a5fa","title":"KANJINTI (TRASTUZUMAB-ANNS) INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION [AMGEN, INC]"},{"url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=7e67e73e-ddf4-4e4d-8b50-09d7514910b6","setid":"7e67e73e-ddf4-4e4d-8b50-09d7514910b6","title":"ENHERTU (FAM-TRASTUZUMAB DERUXTECAN-NXKI) INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION [DAIICHI SANKYO INC.]"},{"url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=ae71c003-883a-4cd8-ad50-e8cc9a54e971","setid":"ae71c003-883a-4cd8-ad50-e8cc9a54e971","title":"HERZUMA (TRASTUZUMAB) KIT HERZUMA (TRASTUZUMAB) INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION [CEPHALON, INC.]"}],"offLabel":[],"synonyms":["trastuzumab-dkst","ogivri","trastuzumab","herceptin","trastuzumab (genetical recombination)"],"timeline":[{"date":"1998-09-25","type":"positive","source":"DrugCentral","milestone":"FDA approval (Genentech)"},{"date":"2000-08-28","type":"positive","source":"DrugCentral","milestone":"EMA approval (Roche Registration Gmbh)"},{"date":"2001-04-04","type":"positive","source":"DrugCentral","milestone":"PMDA approval (Roche Japan)"}],"aiSummary":"KADCYLA is a HER2-targeted antibody-drug conjugate combining trastuzumab with the microtubule inhibitor DM1, indicated for HER2-positive metastatic breast cancer after prior trastuzumab and taxane therapy, and for adjuvant treatment of early breast cancer with residual disease after neoadjuvant therapy. The drug demonstrates a 4-day half-life with linear two-compartment pharmacokinetics and requires CYP3A4 inhibitor avoidance due to increased DM1 exposure risk. Body weight-based dosing of 3.6 mg/kg every 3 weeks is appropriate without adjustment for most covariates. HER2-positive status via FDA-authorized testing is required for patient selection.","brandName":"Herceptin","ecosystem":[],"mechanism":{"target":"HER2 receptor, subdomain IV","novelty":"Follow-on","targets":[{"gene":"ERBB2","source":"DrugCentral","target":"Receptor tyrosine-protein kinase erbB-2","protein":"Receptor tyrosine-protein kinase erbB-2"}],"moaClass":"HER2/Neu/cerbB2 Antagonists","modality":"Monoclonal antibody conjugate","drugClass":"Antibody-drug conjugate (ADC)","explanation":"Ado-trastuzumab emtansine is composed of trastuzumab, a humanized anti-HER2 IgG1 antibody, conjugated to DM1, a small molecule microtubule inhibitor. Upon binding to subdomain IV of the HER2 receptor, the conjugate undergoes receptor-mediated internalization and lysosomal degradation, releasing DM1-containing cytotoxic catabolites intracellularly. DM1 binding to tubulin disrupts microtubule networks, resulting in cell cycle arrest and apoptotic cell death. Additionally, the antibody component inhibits HER2 receptor signaling, mediates antibody-dependent cell-mediated cytotoxicity, and inhibits shedding of the HER2 extracellular domain in HER2-overexpressing breast cancer cells.","oneSentence":"HER2-targeted antibody-drug conjugate delivering microtubule inhibitor DM1 to HER2-overexpressing cells.","technicalDetail":"The humanized anti-HER2 IgG1 antibody (trastuzumab) binds to sub-domain IV of the HER2 receptor, facilitating receptor-mediated internalization and lysosomal degradation. This process releases DM1-containing cytotoxic catabolites, which bind to tubulin and disrupt microtubule networks, causing cell cycle arrest and apoptotic cell death. Ado-trastuzumab emtansine also inhibits HER2 receptor signaling, mediates antibody-dependent cell-mediated cytotoxicity, and inhibits shedding of the HER2 extracellular domain."},"_wikipedia":{"url":"https://en.wikipedia.org/wiki/Trastuzumab","title":"Trastuzumab","extract":"Trastuzumab, sold under the brand name Herceptin among others, is a monoclonal antibody used to treat breast cancer and stomach cancer. It is specifically used for cancer that is HER2 receptor positive. It may be used by itself or together with other chemotherapy medication. Trastuzumab is given by slow injection into a vein and injection just under the skin.","wiki_history":"==History==\nThe drug was first discovered by scientists including Axel Ullrich and H. Michael Shepard at Genentech, Inc. in South San Francisco, CA. Earlier discovery about the neu oncogene by Robert Weinberg's lab and the monoclonal antibody recognizing the oncogenic receptor by Mark Greene's lab also contributed to the establishment of HER2 targeted therapies. Dr. Dennis Slamon subsequently worked on trastuzumab's development. A book about Dr. Slamon's work was made into a television film called Living Proof, that premiered in 2008. Genentech developed trastuzumab jointly with UCLA, beginning the first clinical trial with 15 women in 1992. By 1996, clinical trials had expanded to over 900 women, but due to pressure from advocates based on early success, Genentech worked with the FDA to begin a lottery system allowing 100 women each quarter access to the medication outside the trials. Herceptin was Fast-tracked by the FDA and gained approval in September 1998.","wiki_society_and_culture":"==Society and culture==\n===Economics===\nTrastuzumab costs about for a full course of treatment.\n\nAustralia has negotiated a lower price of A$50,000 per course of treatment.\n\nSince October 2006, trastuzumab has been made available for Australian women and men with early-stage breast cancer via the Pharmaceutical Benefits Scheme. This is estimated to cost the country over A$470 million for 4–5 years supply of the drug.\n\nRoche has agreed with Emcure in India to make an affordable version of this cancer drug available to the Indian market.\n\nRoche has changed the brand name of the drug and has re-introduced an affordable version of the same in the Indian market. The new drug named Herclon would cost approximately RS75,000 INR ( 870) in the Indian market.\n\nOn 16 September 2014, Genentech notified hospitals in the United States that, as of October, trastuzumab could only be purchased through their selected specialty drugs distributors not through the usual general line wholesalers. By being forced to purchase through specialty pharmacies, hospitals lost rebates from the big wholesalers and the ability to negotiate cost-minus discounts with their wholesalers.\n\n===Biosimilars===\n\n\nBy 2014, around 20 companies, particularly from emerging markets, were developing biosimilar versions of trastuzumab\nafter Roche/Genentech's patents expired in 2014 in Europe, and in 2019 in the United States.\n\nIn January 2015, BIOCAD announced the first trastuzumab biosimilar approved by the Ministry of Health of the Russian Federation. Iran also approved its own version of the monoclonal antibody in January 2016, as AryoTrust, and announced its readiness to export the drug to other countries in the Middle-East and Central Asia when trade sanctions were lifted.\n\nIn 2016, the investigational biosimilar MYL-1401O showed comparable efficacy and safety to the Herceptin branded trastuzumab. Trastuzumab-dkst (Ogivri, Mylan GmbH) was approved in the United States in December 2017, to \"treat people wit"},"chemblData":{"prodrug":0,"chemblId":"CHEMBL1201585","maxPhase":"4.0","chirality":1,"parenteral":true,"availability":1,"moleculeType":"Antibody","withdrawnFlag":false,"naturalProduct":0,"blackBoxWarning":1,"oralBioavailable":false},"commercial":{"launchDate":"1998","revenueYear":2024,"_launchSource":"DrugCentral (FDA 1998-09-25, GENENTECH)","annualRevenue":2900,"revenueSource":"Verified: Roche AR","revenueCurrency":"USD","revenueConfidence":"verified"},"fdaRecalls":[],"overdosage":"10 OVERDOSAGE There is no known antidote for overdose of KADCYLA. In clinical trials, overdose of KADCYLA has been reported at approximately two times the recommended dose which resulted in Grade 2 thrombocytopenia (resolved 4 days later) and one death. In the fatal case, the patient incorrectly received KADCYLA at 6 mg/kg and died approximately 3 weeks following the overdose; a cause of death and a causal relationship to KADCYLA were not established.","references":[{"id":1,"url":"https://drugcentral.org/drugcard/4979","fields":["approvals","synonyms","ATC","PK","indications","contraindications","DDIs","targets","patents","FAERS"],"source":"DrugCentral"},{"id":2,"url":"https://clinicaltrials.gov/search?intr=trastuzumab","fields":["trials"],"source":"ClinicalTrials.gov"},{"id":3,"url":"https://pubmed.ncbi.nlm.nih.gov/?term=trastuzumab","fields":["publications"],"source":"PubMed/NCBI"},{"id":4,"url":"https://en.wikipedia.org/wiki/Trastuzumab","fields":["history","overview"],"source":"Wikipedia"}],"_emaChecked":true,"_enrichedAt":"2026-03-29T23:19:21.845224","_validation":{"fieldsValidated":6,"lastValidatedAt":"2026-04-20T08:27:40.128954+00:00","fieldsConflicting":0,"overallConfidence":0.95},"biosimilars":[{"form":"INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION","route":"INTRAVENOUS","company":"Cephalon, Inc.","brandName":"HERZUMA","isOriginal":false,"marketingStatus":"BLA"},{"form":"INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION","route":"INTRAVENOUS","company":"Amgen Inc","brandName":"Kanjinti","isOriginal":false,"marketingStatus":"BLA"},{"form":"INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION","route":"INTRAVENOUS","company":"Biocon Biologics Inc.","brandName":"OGIVRI","isOriginal":false,"marketingStatus":"BLA"},{"form":"INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION","route":"INTRAVENOUS","company":"Merck Sharp & Dohme Corp.","brandName":"Ontruzant","isOriginal":false,"marketingStatus":"BLA"},{"form":"INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION","route":"INTRAVENOUS","company":"Pfizer Laboratories Div Pfizer Inc","brandName":"Trazimera","isOriginal":false,"marketingStatus":"BLA"}],"competitors":[{"drugName":"pertuzumab","drugSlug":"pertuzumab","fdaApproval":"2012-06-08","relationship":"same-class"},{"drugName":"trastuzumab emtansine","drugSlug":"trastuzumab-emtansine","fdaApproval":"2013-02-22","relationship":"same-class"},{"drugName":"trastuzumab deruxtecan","drugSlug":"trastuzumab-deruxtecan","fdaApproval":"2019-12-20","relationship":"same-class"},{"drugName":"margetuximab","drugSlug":"margetuximab","fdaApproval":"2020-12-16","relationship":"same-class"}],"dataSources":[{"url":"https://tavily.com","name":"Tavily AI Search","fields":["latestUpdates"],"retrievedDate":"2026-04-07"},{"url":"https://jina.ai/reader","name":"Jina Reader","fields":["commercialAnalysis"],"retrievedDate":"2026-04-07"},{"url":"https://groq.com","name":"Groq (Llama 3.1 8B)","fields":["commercialAnalysis"],"retrievedDate":"2026-04-07"}],"genericName":"trastuzumab","howSupplied":"16 HOW SUPPLIED/STORAGE AND HANDLING 16.1 How Supplied/Storage KADCYLA (ado-trastuzumab emtansine) is supplied as: Carton Contents NDC One 100 mg vial, single-dose vial NDC 50242-088-01 One 160 mg vial, single-dose vial NDC 50242-087-01 Store vials in a refrigerator at 2°C to 8°C (36°F to 46°F) until time of reconstitution. Do not freeze or shake. 16.2 Special Handling Follow procedures for proper handling and disposal of anticancer drugs.","indications":{"approved":[{"name":"HER2-positive carcinoma of breast","source":"DrugCentral","snomedId":427685000,"regulator":"FDA","globalPrevalence":160000000,"prevalenceMethod":"ai-extracted","prevalenceSource":"Expert Rev Clin Pharmacol, 2019 (PMID:31287333)"},{"name":"HER2-positive colon cancer","source":"DrugCentral","snomedId":363406005,"regulator":"FDA"},{"name":"HER2-positive rectal cancer","source":"DrugCentral","snomedId":363351006,"regulator":"FDA"},{"name":"HER2-positive salivary gland tumors","source":"DrugCentral","snomedId":255072001,"regulator":"FDA"},{"name":"Human epidermal growth factor 2 positive gastric cancer","source":"DrugCentral","snomedId":102453009,"regulator":"FDA"},{"name":"Secondary malignant neoplasm of female breast","source":"DrugCentral","snomedId":94297009,"regulator":"FDA","usPrevalence":null,"globalPrevalence":685000,"prevalenceMethod":"curated","prevalenceSource":"Lancet Oncology, 2023"},{"name":"Secondary malignant neoplasm of stomach","source":"DrugCentral","snomedId":94606003,"regulator":"FDA"}],"offLabel":[],"pipeline":[]},"drugCategory":"active","labelChanges":[],"relatedDrugs":[{"drugId":"pertuzumab","brandName":"pertuzumab","genericName":"pertuzumab","approvalYear":"2012","relationship":"same-class"},{"drugId":"trastuzumab-emtansine","brandName":"trastuzumab emtansine","genericName":"trastuzumab emtansine","approvalYear":"2013","relationship":"same-class"},{"drugId":"trastuzumab-deruxtecan","brandName":"trastuzumab deruxtecan","genericName":"trastuzumab deruxtecan","approvalYear":"2019","relationship":"same-class"},{"drugId":"margetuximab","brandName":"margetuximab","genericName":"margetuximab","approvalYear":"2020","relationship":"same-class"}],"trialDetails":[],"whoEssential":true,"_emaApprovals":[{"date":"2000-08-28","status":"Authorised","company":"ROCHE REGISTRATION GMBH"}],"genericFilers":[],"latestUpdates":[{"url":"https://www.grandviewresearch.com/industry-analysis/herceptin-market-report","date":"2026-04-07","type":"news","title":"Herceptin Market Size, Share & Trends | Industry Report 2030","source":"www.grandviewresearch.com"},{"url":"https://www.coherentmarketinsights.com/industry-reports/herceptin-market","date":"2026-04-07","type":"news","title":"Herceptin Market Size, Opportunities, & YoY Growth Rate, 2033","source":"www.coherentmarketinsights.com"},{"url":"https://www.astrazeneca.com/content/dam/az/PDF/2025/9m-q3/9M-and-Q3-2025-results-announcement.pdf","date":"2026-04-07","type":"news","title":"[PDF] 9M and Q3 2025 results announcement - AstraZeneca","source":"www.astrazeneca.com"},{"url":"https://www.roche.com/media/releases/med-cor-2019-02-28","date":"2026-04-07","type":"news","title":"FDA approves Herceptin Hylecta for subcutaneous injection ... - Roche","source":"www.roche.com"},{"url":"https://www.roche.com/investors/updates/inv-update-2020-02-25","date":"2026-04-07","type":"news","title":"FDA accepts Roche's Biologics License Application for fixed-dose ...","source":"www.roche.com"}],"manufacturing":[],"pivotalTrials":["NCT00950300","NCT01566721","NCT01401166"],"targetProtein":{"url":"https://www.uniprot.org/uniprot/A0A8A0Y2Q6","function":"","geneName":"HER2","organism":"Homo sapiens","uniprotId":"A0A8A0Y2Q6","proteinName":"receptor protein-tyrosine kinase","sequenceLength":53,"molecularWeight":5940,"subcellularLocation":""},"administration":{"route":"Intravenous, Subcutaneous","formulation":"Injection","formulations":[{"form":"INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION","route":"INTRAVENOUS","productName":"HERZUMA"},{"form":"INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION","route":"INTRAVENOUS","productName":"Herceptin"},{"form":"INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION","route":"INTRAVENOUS","productName":"Kanjinti"},{"form":"INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION","route":"INTRAVENOUS","productName":"OGIVRI"},{"form":"INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION","route":"INTRAVENOUS","productName":"Ontruzant"},{"form":"INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION","route":"INTRAVENOUS","productName":"Trazimera"},{"form":"INJECTION, SOLUTION","route":"SUBCUTANEOUS","productName":"Herceptin Hylecta"},{"form":"INJECTION, SOLUTION","route":"SUBCUTANEOUS","productName":"Phesgo"}]},"crossReferences":{"NUI":"N0000148593","MMSL":"11893","NDDF":"007663","UNII":"P188ANX8CK","VUID":"4021140","VANDF":"4021140","INN_ID":"7637","RXNORM":"101306","UMLSCUI":"C0728747","chemblId":"CHEMBL1201585","ChEMBL_ID":"CHEMBL1201585","KEGG_DRUG":"D03257","DRUGBANK_ID":"DB00072","SNOMEDCT_US":"327397006","IUPHAR_LIGAND_ID":"5082","MESH_DESCRIPTOR_UI":"D000068878","MESH_SUPPLEMENTAL_RECORD_UI":"C000630669"},"drugDescription":{"pH":"5.0","structure":"The drug contains the humanized anti-HER2 IgG1, trastuzumab, covalently linked to the microtubule inhibitory drug DM1 (a maytansine derivative) via the stable thioether linker MCC (4-[N-maleimidomethyl] cyclohexane-1-carboxylate). The bracketed structure is DM1 plus MCC which represents the emtansine component. The n is, on average, 3.5 DM1 molecules per trastuzumab (Mab) molecule.","appearance":"KADCYLA (ado-trastuzumab emtansine) is a sterile, white to off-white preservative free lyophilized powder in single-dose vials.","composition":"Ado-trastuzumab emtansine contains an average of 3.5 DM1 molecules per antibody. Each vial contains 100 mg or 160 mg ado-trastuzumab emtansine. Following reconstitution, each single-dose vial contains ado-trastuzumab emtansine (20 mg/mL), polysorbate 20 [0.02% (w/v)], sodium succinate (10 mM), and sucrose [6% (w/v)].","molecularWeight":"","molecularFormula":""},"formularyStatus":[],"originalProduct":{"form":"INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION","route":"INTRAVENOUS","company":"Genentech, Inc.","brandName":"Herceptin","isOriginal":true,"marketingStatus":"BLA"},"_enricherVersion":"v2","chemblMechanisms":[{"actionType":"INHIBITOR","targetChemblId":"CHEMBL1824","mechanismComment":null,"mechanismOfAction":"Receptor protein-tyrosine kinase erbB-2 inhibitor"}],"developmentCodes":[],"ownershipHistory":[],"pharmacokinetics":{"tmax":"close to end of infusion","halfLife":"approximately 4 days","clearance":"0.68 L/day (ADC)","excretion":"","metabolism":"DM1 undergoes metabolism by CYP3A4/5; catabolites MCC-DM1, Lys-MCC-DM1, and DM1 detected at low levels in human plasma","proteinBinding":"93% (DM1 to human plasma proteins)","bioavailability":"","volumeOfDistribution":"3.13 L (central compartment, ADC)"},"publicationCount":15735,"therapeuticAreas":["Oncology"],"_revenueScrapedAt":"2026-04-08 13:57:18.284386+00","atcClassification":{"source":"DrugCentral","atcCode":"L01FD01","allCodes":["L01FD01","L01XY02"]},"biosimilarFilings":[],"faersTotalReports":84473,"commercialAnalysis":{"text":"Herceptin, a monoclonal antibody developed by Roche, is a leading treatment for HER2-positive breast cancer and other cancers. As of 2025, Herceptin generated $2,900 million in revenue [1]. However, the market is expected to decline due to the increasing adoption of biosimilars, which offer more cost-effective alternatives to the original biologic drug [2]. This trend is expected to continue, with the global Herceptin market size projected to reach $1.02 billion by 2033, exhibiting a compound annual growth rate (CAGR) of -5.62% from 2026 to 2033 [3].\n\nThe competitive landscape for Herceptin is becoming increasingly challenging, with emerging biosimilars and evolving treatment protocols impacting the market growth. AstraZeneca's recent results announcement highlights the strong commercial performance of its oncology portfolio, including the growth of its HER2-targeted therapy, Enhertu [4]. This poses a significant threat to Herceptin's market share, particularly in the HER2-positive breast cancer indication.\n\nKey upcoming catalysts for Herceptin include patent cliffs, label expansions, and pipeline competitors. Roche's pipeline includes several promising assets, such as the HER2-targeted therapy, tucatinib, which is currently under investigation for the treatment of HER2-positive breast cancer [5]. Additionally, the FDA has approved several biosimilars for Herceptin, which are expected to further erode the market share of the original biologic drug.\n\nIn conclusion, while Herceptin remains a leading treatment for HER2-positive cancers, the market is expected to decline due to the increasing adoption of biosimilars and evolving treatment protocols. The competitive landscape is becoming increasingly challenging, with emerging biosimilars and pipeline competitors posing a significant threat to Herceptin's market share.\n\nReferences:\n[1] Grand View Research, Herceptin Market Size, Share & Trends | Industry Report 2030\n[2] Coherent Market Insights, Herceptin Market Size, Opportunities, & YoY Growth Rate, 2033\n[3] Coherent Market Insights, Herceptin Market Size, Opportunities, & YoY Growth Rate, 2033\n[4] AstraZeneca, 9M and Q3 2025 results announcement - AstraZeneca\n[5] Roche, Pipeline Overview","model":"llama-3.1-8b (Groq)","sources":[{"url":"https://www.grandviewresearch.com/industry-analysis/herceptin-market-report","date":"","title":"Herceptin Market Size, Share & Trends | Industry Report 2030","source":"www.grandviewresearch.com"},{"url":"https://www.coherentmarketinsights.com/industry-reports/herceptin-market","date":"","title":"Herceptin Market Size, Opportunities, & YoY Growth Rate, 2033","source":"www.coherentmarketinsights.com"},{"url":"https://www.astrazeneca.com/content/dam/az/PDF/2025/9m-q3/9M-and-Q3-2025-results-announcement.pdf","date":"","title":"[PDF] 9M and Q3 2025 results announcement - AstraZeneca","source":"www.astrazeneca.com"}],"disclaimer":"AI-generated analysis based on public sources. 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S, Bones J","journal":"J Am Soc Mass Spectrom","pubDate":"2026 Apr 17"},{"pmid":"41994694","title":"Trastuzumab-Induced Pneumonitis: A Rare but Potentially Severe Pulmonary Complication.","authors":"Rodríguez Sánchez MA, Verdiales Lugo AK, Aguilar Rubio JM, Olguin Guizado CA, Ortiz Jiménez JP","journal":"Cureus","pubDate":"2026 Mar"},{"pmid":"41994032","title":"A prospective, multicenter, observational study of trastuzumab deruxtecan in elderly patients with HER2-positive gastric cancer: EN-COURAGE.","authors":"Narita Y, Kawabata R, Ando T, Arigami T, Kawakami H","journal":"ESMO Gastrointest Oncol","pubDate":"2026 Mar"},{"pmid":"41994020","title":"DESTINY-Gastric05 phase III trial of first-line trastuzumab deruxtecan, chemotherapy, and pembrolizumab in HER2-positive gastric or gastroesophageal junction cancer.","authors":"Janjigian YY, Smyth E, Shen L, Lee J, Hoff PM","journal":"ESMO Gastrointest Oncol","pubDate":"2026 Mar"},{"pmid":"41994003","title":"Impact of claudin 18.2 expression on the efficacy of trastuzumab deruxtecan in patients with HER2-positive gastric or gastroesophageal junction cancer.","authors":"Okemoto D, Nakayama I, Jubashi A, Sakamoto N, Okunaka M","journal":"ESMO Gastrointest Oncol","pubDate":"2026 Mar"},{"pmid":"41993860","title":"Protective effects of beta-blockers against anthracycline- and trastuzumab-related cardiotoxicity: a systematic review based on conventional and Bayesian network meta-analysis.","authors":"Jiang S, Gao G","journal":"Front Cardiovasc Med","pubDate":"2026"},{"pmid":"41989198","title":"Co-reported respiratory adverse events in trastuzumab deruxtecan-associated interstitial lung disease: A pharmacovigilance analysis of the FAERS database.","authors":"Jeral Evinç S, Eyüpler Akmercan Ç, Birsin Z, Cebeci S, Çerme E","journal":"J Oncol Pharm Pract","pubDate":"2026 Apr 16"},{"pmid":"41987583","title":"Cost-effectiveness of pembrolizumab plus trastuzumab and chemotherapy for HER2-positive gastric or gastro-oesophageal junction adenocarcinoma.","authors":"Yu K, Xu Q","journal":"Hum Vaccin Immunother","pubDate":"2026 Dec"},{"pmid":"41980521","title":"Antibody-drug conjugate sequencing in HER2-positive metastatic breast cancer: Real-world outcomes of trastuzumab deruxtecan with and without prior T-DM1 exposure.","authors":"Kemik F, Şahin TK, Özçelik H, Sezer A, Başaran G","journal":"Breast","pubDate":"2026 Apr 10"}],"rxnormFormulations":[{"tty":"SBD","name":"ado-trastuzumab emtansine 100 MG Injection [KADCYLA]","rxcui":"1658087","synonym":"KADCYLA 100 MG Injection"},{"tty":"SBD","name":"ado-trastuzumab emtansine 160 MG Injection [KADCYLA]","rxcui":"1658091","synonym":"KADCYLA 160 MG Injection"},{"tty":"SBD","name":"trastuzumab 150 MG Injection [Herceptin]","rxcui":"1922512","synonym":"Herceptin 150 MG Injection"},{"tty":"SBD","name":"trastuzumab-pkrb 21 MG/ML Injectable Solution [Herzuma]","rxcui":"2107058","synonym":"Herzuma 21 MG/ML Injectable Solution"},{"tty":"SBD","name":"5 ML hyaluronidase-oysk 2000 UNT/ML / trastuzumab-oysk 120 MG/ML Injection [Herceptin Hylecta]","rxcui":"2119719","synonym":"Herceptin Hylecta 600 MG / 10,000 UNT per 5 ML Injection"},{"tty":"SBD","name":"trastuzumab-pkrb 150 MG Injection [Herzuma]","rxcui":"2169362","synonym":"Herzuma 150 MG Injection"},{"tty":"SBD","name":"trastuzumab-anns 21 MG/ML Injectable Solution [Kanjinti]","rxcui":"2174809","synonym":"Kanjinti 21 MG/ML Injectable Solution"},{"tty":"SBD","name":"trastuzumab-dkst 150 MG Injection [Ogivri]","rxcui":"2179758","synonym":"Ogivri 150 MG Injection"},{"tty":"SBD","name":"trastuzumab-dkst 21 MG/ML Injectable Solution [Ogivri]","rxcui":"2179763","synonym":"Ogivri 21 MG/ML Injectable Solution"},{"tty":"SBD","name":"trastuzumab-anns 150 MG Injection [Kanjinti]","rxcui":"2257300","synonym":"Kanjinti 150 MG Injection"},{"tty":"SBD","name":"fam-trastuzumab deruxtecan-nxki 100 MG Injection [Enhertu]","rxcui":"2267581","synonym":"Enhertu 100 MG Injection"},{"tty":"SBD","name":"trastuzumab-qyyp 21 MG/ML Injectable Solution [Trazimera]","rxcui":"2280737","synonym":"Trazimera 21 MG/ML Injectable Solution"},{"tty":"SBD","name":"trastuzumab-dttb 150 MG Injection [Ontruzant]","rxcui":"2289232","synonym":"Ontruzant 150 MG Injection"},{"tty":"SBD","name":"trastuzumab-dttb 21 MG/ML Injectable Solution [Ontruzant]","rxcui":"2289237","synonym":"Ontruzant 21 MG/ML Injectable Solution"},{"tty":"SBD","name":"15 ML hyaluronidase-zzxf 2000 UNT/ML / pertuzumab-zzxf 80 MG/ML / trastuzumab-zzxf 40 MG/ML Injection [Phesgo]","rxcui":"2382609","synonym":"Phesgo 1,200 MG / 600 MG / 30,000 UNT per 15 ML Injection"},{"tty":"SBD","name":"10 ML hyaluronidase-zzxf 2000 UNT/ML / pertuzumab-zzxf 60 MG/ML / trastuzumab-zzxf 60 MG/ML Injection [Phesgo]","rxcui":"2383307","synonym":"Phesgo 600 MG / 600 MG / 20,000 UNT per 10 ML Injection"},{"tty":"SBD","name":"trastuzumab-qyyp 150 MG Injection [Trazimera]","rxcui":"2472794","synonym":"Trazimera 150 MG Injection"},{"tty":"SBD","name":"trastuzumab-strf 150 MG Injection [Hercessi]","rxcui":"2700724","synonym":"Hercessi 150 MG Injection"},{"tty":"SBD","name":"trastuzumab-strf 21 MG/ML Injectable Solution [Hercessi]","rxcui":"2700731","synonym":"Hercessi 21 MG/ML Injectable Solution"},{"tty":"SCD","name":"ado-trastuzumab emtansine 100 MG Injection","rxcui":"1658084","synonym":""},{"tty":"SCD","name":"ado-trastuzumab emtansine 160 MG Injection","rxcui":"1658089","synonym":""},{"tty":"SCD","name":"trastuzumab 150 MG Injection","rxcui":"1922509","synonym":""},{"tty":"SCD","name":"trastuzumab-pkrb 21 MG/ML Injectable Solution","rxcui":"2107053","synonym":"trastuzumab-pkrb 420 MG per 20 ML Injectable Solution"},{"tty":"SCD","name":"5 ML hyaluronidase-oysk 2000 UNT/ML / trastuzumab-oysk 120 MG/ML Injection","rxcui":"2119714","synonym":"trastuzumab-hyaluronidase-oysk 600 MG / 10,000 UNT per 5 ML Injection"},{"tty":"SCD","name":"trastuzumab-pkrb 150 MG Injection","rxcui":"2169359","synonym":""},{"tty":"SCD","name":"trastuzumab-anns 21 MG/ML Injectable Solution","rxcui":"2174804","synonym":"trastuzumab-anns 420 MG per 20 ML Injectable Solution"},{"tty":"SCD","name":"trastuzumab-dkst 150 MG Injection","rxcui":"2179753","synonym":""},{"tty":"SCD","name":"trastuzumab-dkst 21 MG/ML Injectable Solution","rxcui":"2179760","synonym":""},{"tty":"SCD","name":"trastuzumab-anns 150 MG Injection","rxcui":"2257297","synonym":""},{"tty":"SCD","name":"fam-trastuzumab deruxtecan-nxki 100 MG Injection","rxcui":"2267576","synonym":""},{"tty":"SCD","name":"trastuzumab-qyyp 21 MG/ML Injectable Solution","rxcui":"2280732","synonym":"trastuzumab-qyyp 420 MG per 20 ML Injectable Solution"},{"tty":"SCD","name":"trastuzumab-dttb 150 MG Injection","rxcui":"2289227","synonym":""},{"tty":"SCD","name":"trastuzumab-dttb 21 MG/ML Injectable Solution","rxcui":"2289234","synonym":"trastuzumab-dttb 420 MG per 20 ML Injectable Solution"},{"tty":"SCD","name":"15 ML hyaluronidase-zzxf 2000 UNT/ML / pertuzumab-zzxf 80 MG/ML / trastuzumab-zzxf 40 MG/ML Injection","rxcui":"2382604","synonym":"pertuzumab-trastuzumab-hyaluronidase-zzxf 1,200 MG / 600 MG / 30,000 UNT per 15 ML Injection"},{"tty":"SCD","name":"10 ML hyaluronidase-zzxf 2000 UNT/ML / pertuzumab-zzxf 60 MG/ML / trastuzumab-zzxf 60 MG/ML Injection","rxcui":"2383305","synonym":"pertuzumab-trastuzumab-hyaluronidase-zzxf 600 MG / 600 MG / 20,000 UNT per 10 ML Injection"},{"tty":"SCD","name":"trastuzumab-qyyp 150 MG Injection","rxcui":"2472791","synonym":""},{"tty":"SCD","name":"trastuzumab-strf 150 MG Injection","rxcui":"2700718","synonym":""},{"tty":"SCD","name":"trastuzumab-strf 21 MG/ML Injectable Solution","rxcui":"2700727","synonym":"trastuzumab-strf 420 MG per 20 ML Injectable Solution"},{"tty":"SCD","name":"trastuzumab 22 MG/ML Injectable Solution","rxcui":"806573","synonym":"trastuzumab 440 MG per 20 ML Injectable Solution"}],"storageAndHandling":"16.1 How Supplied/Storage KADCYLA (ado-trastuzumab emtansine) is supplied as: Carton Contents NDC One 100 mg vial, single-dose vial NDC 50242-088-01 One 160 mg vial, single-dose vial NDC 50242-087-01 Store vials in a refrigerator at 2°C to 8°C (36°F to 46°F) until time of reconstitution. Do not freeze or shake.","participantFlowData":[],"companionDiagnostics":[{"biomarker":"HER2-positive status","requirement":"required","diagnosticId":"cdx-0","diagnosticName":"FDA-approved test"}],"faersSexDistribution":[{"term":2,"count":67329},{"term":1,"count":5087},{"term":0,"count":488}],"nonclinicalToxicology":"13 NONCLINICAL TOXICOLOGY 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenicity studies have not been conducted with ado-trastuzumab emtansine. DM1 was aneugenic or clastogenic in an in vivo single-dose rat bone marrow micronucleus assay at exposures that were comparable to mean maximum concentrations of DM1 measured in humans administered KADCYLA. DM1 was not mutagenic in an in vitro bacterial reverse mutation (Ames) assay. Based on results from animal toxicity studies, KADCYLA may impair fertility in humans. In a single-dose toxicity study of ado-trastuzumab emtansine in rats, degeneration of seminiferous tubules with hemorrhage in the testes associated with increased weights of testes and epididymides at a severely toxic dose level (60 mg/kg; about 4 times the clinical exposure based on AUC) were observed. The same dose in female rats resulted in signs of hemorrhage and necrosis of the corpus luteum in ovaries. In monkeys dosed with ado-trastuzumab emtansine once every three weeks for 12 weeks (four doses), at up to 30 mg/kg (about 7 times the clinical exposure based on AUC), there were decreases in the weights of epididymides, prostate, testes, seminal vesicles and uterus, although the interpretation of these effects is unclear due to the varied sexual maturity of enrolled animals. 13.2 Animal Toxicology and/or Pharmacology In monkeys, treatment with doses of ado-trastuzumab emtansine up to 30 mg/kg (about 7 times the clinical exposure based on AUC) caused dose dependent axonal degeneration in the sciatic nerve with hypertrophy or hyperplasia of the Schwann cells, and axonal degeneration of the dorsal funiculus in the spinal cord. Based on the mechanism of action of the cytotoxic component DM1, there is clinical potential for neurotoxicity [see Warnings and Precautions (5.8) ].\n13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenicity studies have not been conducted with ado-trastuzumab emtansine. DM1 was aneugenic or clastoge","structuredTrialResults":[],"genericManufacturerList":[],"faersSeriousnessBreakdown":[{"term":1,"count":67394},{"term":2,"count":17068}],"status":"active","companyName":"Roche","companyId":"roche","modality":"Monoclonal antibody","firstApprovalDate":"1998","enrichmentLevel":5,"visitCount":10,"regulatoryByCountry":[{"country_code":"CA","regulator":"Health 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ate":null,"mah":null,"brand_name_local":"Herceptin","application_number":null},{"country_code":"SE","regulator":"MPA","status":"approved","approval_date":null,"mah":null,"brand_name_local":"Herceptin","application_number":null},{"country_code":"US","regulator":"FDA","status":"approved","approval_date":null,"mah":null,"brand_name_local":null,"application_number":null}],"trialStats":{"total":52,"withResults":34},"validation":{"fieldsValidated":6,"lastValidatedAt":"2026-04-20T08:27:40.128954+00:00","fieldsConflicting":0,"overallConfidence":0.95},"verificationStatus":"verified","dataCompleteness":{"mechanism":true,"indications":true,"safety":true,"trials":false,"score":3}}