NCT03493854: FeDeriCa

A Study to Evaluate the Pharmacokinetics, Efficacy, and Safety of Subcutaneous Administration of the Fixed-Dose Combination of Pertuzumab and Trastuzumab in Combination With Chemotherapy in Participants With HER2-Positive Early Breast Cancer

Completed Phase 3 Results posted Last updated 26 June 2024

What this trial tests

Phase 3 trial testing Cyclophosphamide in Early Breast Cancer in 500 participants. Completed in 2 June 2023.

Timeline

14 June 2018

Primary endpoint
4 July 2019

2 June 2023

Quick facts

Lead sponsor	Hoffmann-La Roche
Phase	Phase 3
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	none
Primary purpose	treatment
Enrollment	500
Start date	14 June 2018
Primary completion	4 July 2019
Estimated completion	2 June 2023
Sites	107 locations across Italy, Japan, Taiwan, Poland, South Korea, Russia, Belgium, Mexico

Drugs / interventions tested

• Cyclophosphamide (cyclophosphamide) — full drug profile →
• Doxorubicin
• Docetaxel
• Paclitaxel — full drug profile →
• Pertuzumab IV — full drug profile →
• FDC of Pertuzumab and Trastuzumab SC — full drug profile →
• Trastuzumab IV
• Trastuzumab SC
• Surgery
• Post-operative Radiotherapy
• Hormone Therapy

Conditions studied

• Early Breast Cancer — all drugs for Early Breast Cancer →

Sponsor

Hoffmann-La Roche — full company profile →

Who can join

18 and older, any sex, with Early Breast Cancer. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Trough Serum Concentration (Ctrough) of Pertuzumab During Cycle 7 (Pre-Dose Cycle 8) Primary · Pre-dose on Cycle 8, Day 1 (up to 21 weeks)

The observed pertuzumab trough serum concentration (Ctrough) at Cycle 7 was assessed following 3 cycles of pertuzumab IV and trastuzumab IV or the fixed-dose combination (FDC) of pertuzumab and trastuzumab SC. The Per Protocol Pharmacokinetics (PK) analysis population includes all enrolled participants who adhered to the protocol. Exclusions from the Per Protocol PK analysis population were made for the following reasons: participants were missing the Ctrough pre-dose Cycle 8 PK sample, participants with a Ctrough sample collected with at least 2 days deviation from the planned date on Day 21

Group	Value	95% CI
Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy	72.4	± 34.1
Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy	88.7	± 33.6

Ctrough of Trastuzumab During Cycle 7 (Pre-Dose Cycle 8) Secondary · Pre-dose on Cycle 8, Day 1 (up to 21 weeks)

The observed trastuzumab trough serum concentration (Ctrough) at Cycle 7 was assessed following 3 cycles of pertuzumab IV and trastuzumab IV or the fixed-dose combination (FDC) of pertuzumab and trastuzumab SC. The Per Protocol Pharmacokinetics (PK) analysis population includes all enrolled participants who adhered to the protocol. Exclusions from the Per Protocol PK analysis population were made for the following reasons: participants were missing the Ctrough pre-dose Cycle 8 PK sample, participants with a Ctrough sample collected with at least 2 days deviation from the planned date on Day 21

Group	Value	95% CI
Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy	43.2	± 34.7
Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy	57.5	± 37.0

Percentage of Participants With Total Pathological Complete Response (tpCR), According to Local Pathologist Assessment Secondary · Following completion of surgery (up to 33 weeks)

Total pCR (tpCR) was defined as eradication of invasive disease in the breast and axilla; that is, ypT0/is ypN0, according to the local pathologists' assessment. Pathologic response to therapy was determined at the time of surgery. The tpCR rate is the percentage of participants in the ITT population who achieved a tpCR. Participants with missing data for tpCR (i.e., do not undergo surgery or have an invalid pCR assessment) were included in the analysis and classified as non-responders. Rates of tpCR were calculated in each treatment arm and were assessed using the difference between the Arm B

Group	Value	95% CI
Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy	59.5	53.2 – 65.6
Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy	59.7	53.3 – 65.8

Kaplan-Meier Estimate of the Percentage of Participants Who Are Event-Free According to Invasive Disease-Free Survival (iDFS; Excluding Second Primary Non-Breast Cancer [SPNBC]) Criteria Secondary · At 1, 2, 3, and 4 years

iDFS (excluding SPNBC) is defined as the time from the first date of no disease (i.e., the date of primary surgery) to the first occurrence of one of the following events: ipsilateral invasive breast tumor recurrence; ipsilateral local-regional invasive breast cancer reccurrence; distant recurrence; contralateral invasive breast cancer; or death attributable to any cause. Ipsilateral or contralateral in situ disease and SPNBC (including in situ carcinomas and non-melanoma skin cancers) will not be counted as progressive disease or relapse.

1 Year

Group	Value	95% CI
Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy	96.07	93.55 – 98.59
Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy	97.37	95.30 – 99.45

2 Years

Group	Value	95% CI
Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy	92.98	89.66 – 96.30
Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy	90.75	86.98 – 94.52

3 Years

Group	Value	95% CI
Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy	90.71	86.93 – 94.50
Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy	89.86	85.93 – 93.79

4 Years

Group	Value	95% CI
Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy	89.60	85.54 – 93.65
Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy	88.50	84.34 – 92.66

Kaplan-Meier Estimate of the Percentage of Participants Who Are Event-Free According to iDFS (Including SPNBC) Criteria Secondary · At 1, 2, 3, and 4 years

Invasive disease-free survival (iDFS) including second primary non-breast cancer (SPNBC) is defined as the time from the first date of no disease (i.e., the date of primary surgery) to the first occurrence of one of the following events: ipsilateral invasive breast tumor recurrence; ipsilateral local-regional invasive breast cancer reccurrence; distant recurrence; contralateral invasive breast cancer; or death attributable to any cause. It also includes SPNBC as an event (with the exception of non-melanoma skin cancers and in situ carcinoma of any site).

1 Year

Group	Value	95% CI
Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy	95.63	92.99 – 98.28
Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy	96.94	94.70 – 99.17

2 Years

Group	Value	95% CI
Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy	92.10	88.60 – 95.60
Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy	89.44	85.44 – 93.43

3 Years

Group	Value	95% CI
Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy	89.39	85.37 – 93.40
Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy	88.54	84.40 – 92.69

4 Years

Group	Value	95% CI
Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy	88.27	84.01 – 92.53
Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy	87.64	83.35 – 91.93

Kaplan-Meier Estimate of the Percentage of Participants Who Are Event-Free According to Event-Free Survival (EFS; Excluding SPNBC) Criteria Secondary · At 1, 2, 3, and 4 years

Event-free survival (EFS) excluding second primary non-breast cancer (SPNBC) is defined as the time from enrollment to the first occurrence of one of the following events: breast cancer progression; breast cancer recurrence; or death from any cause. Ipsilateral or contralateral in situ disease and SPNBC (including in situ carcinomas and non-melanoma skin cancers) will not be counted as progressive disease or relapse.

1 Year

Group	Value	95% CI
Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy	96.79	94.60 – 98.98
Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy	97.95	96.18 – 99.73

2 Years

Group	Value	95% CI
Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy	92.29	88.96 – 95.62
Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy	91.67	88.17 – 95.16

3 Years

Group	Value	95% CI
Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy	89.77	85.96 – 93.57
Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy	88.29	84.21 – 92.37

4 Years

Group	Value	95% CI
Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy	88.47	84.44 – 92.49
Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy	86.57	82.24 – 90.90

Kaplan-Meier Estimate of the Percentage of Participants Who Are Event-Free According to EFS (Including SPNBC) Criteria Secondary · At 1, 2, 3, and 4 years

Event-free survival (EFS) including second primary non-breast cancer (SPNBC) is defined as the time from enrollment to the first occurrence of one of the following events: breast cancer progression; breast cancer recurrence; or death from any cause. It also includes SPNBC as an event (with the exception of non-melanoma skin cancers and in situ carcinoma of any site).

1 Year

Group	Value	95% CI
Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy	96.38	94.06 – 98.70
Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy	97.54	95.59 – 99.48

2 Years

Group	Value	95% CI
Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy	91.47	87.98 – 94.96
Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy	90.41	86.69 – 94.14

3 Years

Group	Value	95% CI
Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy	88.53	84.52 – 92.53
Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy	87.04	82.78 – 91.30

4 Years

Group	Value	95% CI
Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy	87.22	83.02 – 91.43
Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy	85.75	81.31 – 90.18

Kaplan-Meier Estimate of the Percentage of Participants Who Are Event-Free According to Distant Recurrence-Free Interval (DRFI) Criteria Secondary · At 1, 2, 3, and 4 years

The distant recurrence-free interval (DRFI) is defined as the time between randomization and the date of distant breast cancer recurrence.

1 Year

Group	Value	95% CI
Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy	99.59	98.80 – 100.00
Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy	99.58	98.77 – 100.00

2 Years

Group	Value	95% CI
Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy	95.88	93.39 – 98.38
Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy	95.37	92.70 – 98.04

3 Years

Group	Value	95% CI
Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy	93.77	90.72 – 96.82
Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy	93.23	90.02 – 96.43

4 Years

Group	Value	95% CI
Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy	92.49	89.15 – 95.83
Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy	91.92	88.44 – 95.41

Kaplan-Meier Estimate of the Percentage of Participants in Overall Survival Secondary · At 1, 2, 3, and 4 years

Overall survival is defined as the time from randomization to death from any cause.

1 Year

Group	Value	95% CI
Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy	99.60	98.82 – 100.00
Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy	99.19	98.06 – 100.00

2 Years

Group	Value	95% CI
Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy	98.38	96.80 – 99.95
Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy	96.68	94.42 – 98.94

3 Years

Group	Value	95% CI
Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy	96.73	94.50 – 98.96
Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy	95.83	93.30 – 98.36

4 Years

Group	Value	95% CI
Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy	95.47	92.86 – 98.09
Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy	94.13	91.14 – 97.11

Summary of the Number of Participants With at Least One Adverse Event, Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI CTCAE v4.0), Over the Course of the Entire Study Secondary · From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months)

The adverse event (AE) severity grading scale for the NCI CTCAE v4.0 was used for assessing AE severity. Any AEs that were not specifically listed in the NCI CTCAE, v4.0 were graded per the following 5 grades: Grade 1 = mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; or intervention not indicated. Grade 2 = moderate; minimal, local, or non-invasive intervention indicated; or limiting age-appropriate instrumental activities of daily living. Grade 3 = severe or medically significant, but not immediately life-threatening; hospitalization or prolongation of hospitali

Any Adverse Event (AE): Any Grade

Group	Value	95% CI
Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy	251
Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy	248

AE with Fatal Outcome (Grade 5)

Group	Value	95% CI
Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy	2
Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy	2

Any AE: Grades 3 to 5

Group	Value	95% CI
Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy	149
Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy	132

Serious AE

Group	Value	95% CI
Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy	52
Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy	49

Related Serious AE

Group	Value	95% CI
Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy	29
Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy	29

Anaphylaxis and Hypersensitivity AEs, Any Grade

Group	Value	95% CI
Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy	3
Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy	3

Anaphylaxis and Hypersensitivity AEs, Grade ≥3

Group	Value	95% CI
Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy	1
Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy	0

Infusion/Admin.-Related Reactions Within 24 hrs, Any Grade

Group	Value	95% CI
Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy	39
Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy	54

Number of Participants With a Primary Cardiac Event During the Neoadjuvant Phase Secondary · From first dose of study treatment until the completion of neoadjuvant therapy (24 weeks)

A primary cardiac event is defined as the occurrence of either of the following events: - Incidence of a symptomatic ejection fraction decrease (heart failure) of New York Heart Association (NYHA) Class III or IV and a drop in left ventricular ejection fraction (LVEF) of at least 10-percentage points from baseline and to below 50%; or - Cardiac death, defined as: Definite cardiac death (due to heart failure, myocardial infarction, or documented primary arrhythmia); or, Probable cardiac death (sudden unexpected death within 24 hours of a definite or probable cardiac event \[e.g., syncope, cardi

Any Primary Cardiac Event

Group	Value	95% CI
Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy	0
Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy	2

Heart Failure and Significant LVEF Decline

Group	Value	95% CI
Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy	0
Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy	1

Cardiac Death (Definite or Probable)

Group	Value	95% CI
Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy	0
Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy	1

Number of Participants With a Secondary Cardiac Event During the Neoadjuvant Phase Secondary · From first dose of study treatment until the completion of neoadjuvant therapy (24 weeks)

A secondary cardiac event is defined as asymptomatic or mildly symptomatic Left Ventricular Systolic Dysfunction (LVSD) of NYHA Class II, defined as a left ventricular ejection fraction (LVEF) decrease of at least 10-percentage points below the baseline measurement to an absolute LVEF value of \<50% confirmed by a second assessment within approximately 3 weeks.

Any Secondary Cardiac Event

Group	Value	95% CI
Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy	4
Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy	1

Identified by Initial LVEF Assessment

Group	Value	95% CI
Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy	4
Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy	1

Confirmed by Second LVEF Assessment

Group	Value	95% CI
Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy	1
Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy	1

Adverse events — posted to ClinicalTrials.gov

Time frame: Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months). Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy

Serious: 52/252 (21%)

Deaths: 12/252

Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy

Serious: 49/248 (20%)

Deaths: 14/248

Serious adverse events (79 terms)

Reaction	System	Arm A: Pertuzumab IV + Tra…	Arm B: Pertuzumab and Tras…
Febrile neutropenia	Blood and lymphatic system disorders	—	—
Cardiac failure	Cardiac disorders	—	—
Neutropenia	Blood and lymphatic system disorders	—	—
Pyrexia	General disorders	—	—
Neutropenic sepsis	Infections and infestations	—	—
Pneumonia	Infections and infestations	—	—
Neutrophil count decreased	Investigations	—	—
Diarrhoea	Gastrointestinal disorders	—	—
Mastitis	Infections and infestations	—	—
Postoperative wound infection	Infections and infestations	—	—
Sepsis	Infections and infestations	—	—
Infusion related reaction	Injury, poisoning and procedural complications	—	—
Pneumonitis	Respiratory, thoracic and mediastinal disorders	—	—
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	—	—
Anaemia	Blood and lymphatic system disorders	—	—
Immune thrombocytopenia	Blood and lymphatic system disorders	—	—
Acute myocardial infarction	Cardiac disorders	—	—
Arrhythmia	Cardiac disorders	—	—
Cardiomyopathy	Cardiac disorders	—	—
Goitre	Endocrine disorders	—	—
Abdominal pain	Gastrointestinal disorders	—	—
Anal incontinence	Gastrointestinal disorders	—	—
Colitis	Gastrointestinal disorders	—	—
Gastritis haemorrhagic	Gastrointestinal disorders	—	—
Gastrointestinal toxicity	Gastrointestinal disorders	—	—

Other adverse events (74 terms — click to expand)

Reaction	System	Arm A: Pertuzumab IV + Tra…	Arm B: Pertuzumab and Tras…
Alopecia	Skin and subcutaneous tissue disorders	—	—
Nausea	Gastrointestinal disorders	—	—
Diarrhoea	Gastrointestinal disorders	—	—
Anaemia	Blood and lymphatic system disorders	—	—
Asthenia	General disorders	—	—
Arthralgia	Musculoskeletal and connective tissue disorders	—	—
Fatigue	General disorders	—	—
Headache	Nervous system disorders	—	—
Myalgia	Musculoskeletal and connective tissue disorders	—	—
Neutropenia	Blood and lymphatic system disorders	—	—
Stomatitis	Gastrointestinal disorders	—	—
Constipation	Gastrointestinal disorders	—	—
Rash	Skin and subcutaneous tissue disorders	—	—
Radiation skin injury	Injury, poisoning and procedural complications	—	—
Neutrophil count decreased	Investigations	—	—
Decreased appetite	Metabolism and nutrition disorders	—	—
Vomiting	Gastrointestinal disorders	—	—
Alanine aminotransferase increased	Investigations	—	—
Mucosal inflammation	General disorders	—	—
Insomnia	Psychiatric disorders	—	—
Dysgeusia	Nervous system disorders	—	—
Peripheral sensory neuropathy	Nervous system disorders	—	—
Pyrexia	General disorders	—	—
Cough	Respiratory, thoracic and mediastinal disorders	—	—
Hot flush	Vascular disorders	—	—
Injection site reaction	General disorders	—	—
Aspartate aminotransferase increased	Investigations	—	—
Neuropathy peripheral	Nervous system disorders	—	—
Dry skin	Skin and subcutaneous tissue disorders	—	—
Epistaxis	Respiratory, thoracic and mediastinal disorders	—	—
Leukopenia	Blood and lymphatic system disorders	—	—
Nasopharyngitis	Infections and infestations	—	—
Infusion related reaction	Injury, poisoning and procedural complications	—	—
Dyspepsia	Gastrointestinal disorders	—	—
White blood cell count decreased	Investigations	—	—
Upper respiratory tract infection	Infections and infestations	—	—
Dizziness	Nervous system disorders	—	—
Procedural pain	Injury, poisoning and procedural complications	—	—
Dyspnoea	Respiratory, thoracic and mediastinal disorders	—	—
Pruritus	Skin and subcutaneous tissue disorders	—	—

Most-reported serious reactions: Febrile neutropenia, Cardiac failure, Neutropenia, Pyrexia, Neutropenic sepsis, Pneumonia, Neutrophil count decreased, Diarrhoea.

Data from ClinicalTrials.gov NCT03493854 adverse events section.

Sponsor's own description

This is a global Phase III, two-arm, open-label, multicenter, randomized study to investigate the pharmacokinetics, efficacy, and safety of the fixed-dose combination (FDC) of pertuzumab and trastuzumab for subcutaneous (SC) administration in combination with chemotherapy in patients with human epidermal growth factor receptor 2 (HER2)-positive early breast cancer in the neoadjuvant/adjuvant setting.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Role of tumor microenvironment in cancer progression and therapeutic strategy.
   Wang Q, Shao X, Zhang Y, Zhu M, et al · · 2023 · cited 260× · PMID 36807772 · DOI 10.1002/cam4.5698
2. Understanding and targeting resistance mechanisms in cancer.
   Lei ZN, Tian Q, Teng QX, Wurpel JND, et al · · 2023 · cited 174× · PMID 37229486 · DOI 10.1002/mco2.265
3. Fixed-dose combination of pertuzumab and trastuzumab for subcutaneous injection plus chemotherapy in HER2-positive early breast cancer (FeDeriCa): a randomised, open-label, multicentre, non-inferiority, phase 3 study.
   Tan AR, Im SA, Mattar A, Colomer R, et al · · 2021 · cited 117× · PMID 33357420 · DOI 10.1016/s1470-2045(20)30536-2
4. HER2-targeted therapies in cancer: a systematic review.
   Zhu K, Yang X, Tai H, Zhong X, et al · · 2024 · cited 83× · PMID 38308374 · DOI 10.1186/s40364-024-00565-1
5. Flexible care in breast cancer.
   Wardley A, Canon JL, Elsten L, Peña Murillo C, et al · · 2021 · cited 18× · PMID 33450658 · DOI 10.1016/j.esmoop.2020.100007
6. Population pharmacokinetic and exploratory exposure-response analysis of the fixed-dose combination of pertuzumab and trastuzumab for subcutaneous injection in patients with HER2-positive early breast cancer in the FeDeriCa study.
   Wang B, Deng R, Hennig S, Badovinac Crnjevic T, et al · · 2021 · cited 10× · PMID 34106303 · DOI 10.1007/s00280-021-04296-0
7. Incidence and severity of anaphylaxis and hypersensitivity in trials of intravenous pertuzumab plus trastuzumab or the fixed-dose combination of pertuzumab and trastuzumab for subcutaneous injection for HER2-positive breast cancer.
   Swain SM, Tan AR, Gianni L, Kuemmel S, et al · · 2023 · cited 4× · PMID 36410207 · DOI 10.1016/j.ejca.2022.09.024
8. Biomaterials' enhancement of immunotherapy for breast cancer by targeting functional cells in the tumor micro-environment.
   Santerre JP, Yang Y, Du Z, Wang W, et al · · 2024 · cited 3× · PMID 39600709 · DOI 10.3389/fimmu.2024.1492323