NCT03043313

Tucatinib Plus Trastuzumab in Patients With HER2+ Colorectal Cancer

Completed Phase 2 Results posted Last updated 26 November 2024

What this trial tests

Phase 2 trial testing Trastuzumab in Metastatic Colorectal Adenocarcinoma in 117 participants. Completed in 2 November 2023.

Timeline

23 June 2017

Primary endpoint
28 March 2022

2 November 2023

Quick facts

Lead sponsor	Seagen Inc.
Phase	Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	none
Primary purpose	treatment
Enrollment	117
Start date	23 June 2017
Primary completion	28 March 2022
Estimated completion	2 November 2023
Sites	56 locations across France, Italy, Belgium, United States, Spain

Drugs / interventions tested

• Trastuzumab (trastuzumab) — full drug profile →
• Tucatinib (tucatinib) — full drug profile →

Conditions studied

• Metastatic Colorectal Adenocarcinoma — all drugs for Metastatic Colorectal Adenocarcinoma →

Sponsor

Seagen Inc. — full company profile →

Who can join

18 and older, any sex, with Metastatic Colorectal Adenocarcinoma. 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.

Confirmed Objective Response Rate (cORR) Per RECIST v1.1 Per Blinded Independent Central Review (BICR) in Pooled Cohorts A+B Primary · Up to 46.6 months

cORR was defined as the percentage of participants with confirmed CR or PR according to RECIST v1.1. CR was defined as the disappearance of all target lesions and each target lymph node must have reduction in short axis to less than (\<)1.0 centimeter (cm). PR was defined as at least a 30 percentage (%) decrease in post-baseline sum of the diameters (sum of the longest diameter for all target lesions plus the sum of the short axis of all the target lymph nodes at current evaluation) taking as reference the baseline sum of diameters.

Group	Value	95% CI
Tucatinib+Trastuzumab (Cohorts A+B)	39.3	28.8 – 50.5

ORR by 12 Weeks of Treatment Per RECIST v1.1 According to BICR Assessment Secondary · Up to 3 months

ORR per BICR by 12 Weeks was defined as the percentage of participants with CR or PR by 12 weeks of treatment, and before time of crossover (Cohort C), whichever came earlier. CR was defined as the disappearance of all target lesions and each target lymph node must have reduction in short axis to more than \<1.0 cm. PR was defined as at least a 30% decrease in post-baseline sum of the diameters (sum of the longest diameter for all target lesions plus the sum of the short axis of all the target lymph nodes at current evaluation) taking as reference the baseline sum of diameter.

Group	Value	95% CI
Tucatinib+Trastuzumab (Cohorts A+B)	28.6	19.2 – 39.5
Tucatinib Pre-Crossover (Cohort C)	3.3	0.1 – 17.2

Duration of Response (DOR) Per RECIST v1.1 According to BICR Assessment Secondary · Up to 64.1 months

DOR was defined as the time from the first objective response (CR or PR that is subsequently confirmed) to documented PD per RECIST v1.1 or death from any cause, whichever occurred first. CR was defined as the disappearance of all target lesions and each target lymph node must have reduction in short axis to more than \<1.0 cm. PR was defined as at least a 30% decrease in post-baseline sum of the diameters (PBSD) (sum of the longest diameter for all target lesions plus the sum of the short axis of all the target lymph nodes at current evaluation) taking as reference the BSD. PD was defined as:

Group	Value	95% CI
Tucatinib+Trastuzumab (Cohorts A+B)	15.2	8.9 – 20.5
Tucatinib Pre-Crossover (Cohort C)	NA	NA – NA

Progression-Free Survival (PFS) Per RECIST v1.1 According to BICR Assessment for Pooled Cohorts A+B Secondary · Up to 64.1 months

PFS was defined as the time from start of study treatment (Cohort A) or date of randomization (Cohort B) to documented disease progression (as determined by BICR per RECIST v1.1) or death from any cause, whichever occurred first. PD was defined as: at least one new malignant lesion, which also included any lymph node that was normal at baseline (\<1.0 cm short axis) and increased to \>=1.0 cm short axis during follow-up or at least a 20% increase in post-baseline sum of the diameters (PBSD) taking as reference the minimum sum of the diameters (MSD). In addition, the PBSD must also demonstrate

Group	Value	95% CI
Tucatinib+Trastuzumab (Cohorts A+B)	8.1	4.2 – 10.2

Overall Survival (OS) in Pooled Cohorts A+B Secondary · Up to 71.8 months

OS was defined as the time from start of study treatment (Cohort A) or randomization (Cohort B) to date of death due to any cause.

Group	Value	95% CI
Tucatinib+Trastuzumab (Cohorts A+B)	23.9	18.7 – 28.3

Number of Participants With Adverse Events (AEs): Interim Analysis Secondary · Up to 49.3 months

AE: Any untoward medical occurrence in a participant or clinical investigational participant administered a medicinal product and which does not necessarily have a causal relationship with this treatment. Treatment emergent AEs (TEAEs): Events that were new or worsened on or after receiving the first dose of study treatment (tucatinib or trastuzumab) and up through 30 days after the last dose of study treatment (tucatinib or trastuzumab). Serious AE (SAE): An event that at any dose led to death; life-threatening; required inpatient hospitalization/prolongation of existing hospitalization; pers

Any TEAE

Group	Value	95% CI
Tucatinib+Trastuzumab (Cohorts A+B)	82
Tucatinib Pre-Crossover (Cohort C)	28

Tucatinib-related TEAE

Group	Value	95% CI
Tucatinib+Trastuzumab (Cohorts A+B)	63
Tucatinib Pre-Crossover (Cohort C)	22

Trastuzumab-related TEAE

Group	Value	95% CI
Tucatinib+Trastuzumab (Cohorts A+B)	58
Tucatinib Pre-Crossover (Cohort C)	NA

Any grade 3-5 TEAE

Group	Value	95% CI
Tucatinib+Trastuzumab (Cohorts A+B)	33
Tucatinib Pre-Crossover (Cohort C)	8

Trastuzumab-related grade 3-5 TEAE

Group	Value	95% CI
Tucatinib+Trastuzumab (Cohorts A+B)	6
Tucatinib Pre-Crossover (Cohort C)	NA

Tucatinib-related grade 3-5 TEAE

Group	Value	95% CI
Tucatinib+Trastuzumab (Cohorts A+B)	8
Tucatinib Pre-Crossover (Cohort C)	2

Any Treatment-Emergent Serious AE (TESAE)

Group	Value	95% CI
Tucatinib+Trastuzumab (Cohorts A+B)	19
Tucatinib Pre-Crossover (Cohort C)	3

Tucatinib-related TESAE

Group	Value	95% CI
Tucatinib+Trastuzumab (Cohorts A+B)	3
Tucatinib Pre-Crossover (Cohort C)	1

Number of Participants With AEs: Final Analysis Secondary · Up to 65.1 months

AE: Any untoward medical occurrence in a participant or clinical investigational participant administered a medicinal product and which does not necessarily have a causal relationship with this treatment. Treatment emergent AEs (TEAEs): Events that were new or worsened on or after receiving the first dose of study treatment (tucatinib or trastuzumab) and up through 30 days after the last dose of study treatment (tucatinib or trastuzumab). SAE: An event that at any dose led to death; life-threatening; required inpatient hospitalization/prolongation of existing hospitalization; persistent/signif

Any TEAE

Group	Value	95% CI
Tucatinib+Trastuzumab (Cohorts A+B)	82
Tucatinib Post-Crossover (Cohort C)	23

Tucatinib-related TEAE

Group	Value	95% CI
Tucatinib+Trastuzumab (Cohorts A+B)	64
Tucatinib Post-Crossover (Cohort C)	15

Trastuzumab-related TEAE

Group	Value	95% CI
Tucatinib+Trastuzumab (Cohorts A+B)	59
Tucatinib Post-Crossover (Cohort C)	13

More than or equal to (>=) Grade 3 TEAE

Group	Value	95% CI
Tucatinib+Trastuzumab (Cohorts A+B)	35
Tucatinib Post-Crossover (Cohort C)	9

Tucatinib-related >= grade 3 TEAE

Group	Value	95% CI
Tucatinib+Trastuzumab (Cohorts A+B)	8
Tucatinib Post-Crossover (Cohort C)	2

Trastuzumab-related >= grade 3 TEAE

Group	Value	95% CI
Tucatinib+Trastuzumab (Cohorts A+B)	6
Tucatinib Post-Crossover (Cohort C)	2

Any Treatment-Emergent Serious AE (TESAE)

Group	Value	95% CI
Tucatinib+Trastuzumab (Cohorts A+B)	20
Tucatinib Post-Crossover (Cohort C)	6

Tucatinib-related TESAE

Group	Value	95% CI
Tucatinib+Trastuzumab (Cohorts A+B)	3
Tucatinib Post-Crossover (Cohort C)	0

Number of Participants With AEs Resulting in Dose Modification: Interim Analysis Secondary · Up to 49.3 months

Dose modification included dose reduction and dose withheld by investigator due to AEs. Dose holds were defined as any instances where planned administration of the study drug was temporarily withheld or interrupted at the direction of the treating physician. Dose reductions of trastuzumab were not allowed; if trastuzumab could not be restarted after being held for a TEAE, it was discontinued.

Tucatinib dose held

Group	Value	95% CI
Tucatinib+Trastuzumab (Cohorts A+B)	20
Tucatinib Pre-Crossover (Cohort C)	3

Tucatinib dose reduced

Group	Value	95% CI
Tucatinib+Trastuzumab (Cohorts A+B)	8
Tucatinib Pre-Crossover (Cohort C)	1

Trastuzumab dose held

Group	Value	95% CI
Tucatinib+Trastuzumab (Cohorts A+B)	24
Tucatinib Pre-Crossover (Cohort C)	NA

Trastuzumab infusion interrupted (received full dose within 24 hrs)

Group	Value	95% CI
Tucatinib+Trastuzumab (Cohorts A+B)	6
Tucatinib Pre-Crossover (Cohort C)	NA

Trastuzumab infusion stopped early (full dose not received)

Group	Value	95% CI
Tucatinib+Trastuzumab (Cohorts A+B)	1
Tucatinib Pre-Crossover (Cohort C)	NA

Number of Participants With AEs Resulting in Dose Modification: Final Analysis Secondary · Up to 65.1 months

Dose modification included dose reduction and dose withheld by investigator due to AEs. Dose holds were defined as any instances where planned administration of the study drug was temporarily withheld or interrupted at the direction of the treating physician. Dose reductions of trastuzumab were not allowed; if trastuzumab could not be restarted after being held for a TEAE, it was discontinued. Drug interruption included infusion interrupted (full dose received within 24hrs).

Tucatinib dose held

Group	Value	95% CI
Tucatinib+Trastuzumab (Cohorts A+B)	23
Tucatinib Post-Crossover (Cohort C)	7

Tucatinib dose reduced

Group	Value	95% CI
Tucatinib+Trastuzumab (Cohorts A+B)	9
Tucatinib Post-Crossover (Cohort C)	2

Trastuzumab dose held

Group	Value	95% CI
Tucatinib+Trastuzumab (Cohorts A+B)	27
Tucatinib Post-Crossover (Cohort C)	2

Trastuzumab infusion interrupted

Group	Value	95% CI
Tucatinib+Trastuzumab (Cohorts A+B)	6
Tucatinib Post-Crossover (Cohort C)	0

Number of Participants With Treatment-Emergent Laboratory Abnormalities (Hematology): Interim Analysis Secondary · Up to 49.3 months

The following hematology laboratory parameters were assessed: Hemoglobin decreased; leukocytes decreased; neutrophils decreased and Platelets decreased. Treatment emergent laboratory abnormalities were defined as abnormalities that were new or worsened on or after receiving the first dose of study treatment and up through 30 days after the last dose of study treatment. NCI CTCAE v4.03 was used for the lab parameters. Grade 1: mild; Grade 2: moderate; Grade 3: severe or clinically significant; Grade 4: life-threatening.

Hemoglobin decreased, Grade 1

Group	Value	95% CI
Tucatinib+Trastuzumab (Cohorts A+B)	28
Tucatinib Pre-Crossover (Cohort C)	6

Hemoglobin decreased, Grade 2

Group	Value	95% CI
Tucatinib+Trastuzumab (Cohorts A+B)	8
Tucatinib Pre-Crossover (Cohort C)	2

Hemoglobin decreased, Grade 3

Group	Value	95% CI
Tucatinib+Trastuzumab (Cohorts A+B)	3
Tucatinib Pre-Crossover (Cohort C)	0

Hemoglobin decreased, Grade 4

Group	Value	95% CI
Tucatinib+Trastuzumab (Cohorts A+B)	0
Tucatinib Pre-Crossover (Cohort C)	0

Leukocytes decreased, Grade 1

Group	Value	95% CI
Tucatinib+Trastuzumab (Cohorts A+B)	14
Tucatinib Pre-Crossover (Cohort C)	3

Leukocytes decreased, Grade 2

Group	Value	95% CI
Tucatinib+Trastuzumab (Cohorts A+B)	5
Tucatinib Pre-Crossover (Cohort C)	0

Leukocytes decreased, Grade 3

Group	Value	95% CI
Tucatinib+Trastuzumab (Cohorts A+B)	0
Tucatinib Pre-Crossover (Cohort C)	0

Leukocytes decreased, Grade 4

Group	Value	95% CI
Tucatinib+Trastuzumab (Cohorts A+B)	0
Tucatinib Pre-Crossover (Cohort C)	0

Number of Participants With Treatment-Emergent Laboratory Abnormalities (Hematology): Final Analysis Secondary · Up to 65.1 months

The following hematology laboratory parameters were assessed: Hemoglobin decreased; hemoglobin increased; leukocytes decreased; lymphocytes decreased; neutrophils decreased and Platelets decreased. Treatment emergent laboratory abnormalities were defined as abnormalities that were new or worsened on or after receiving the first dose of study treatment and up through 30 days after the last dose of study treatment. NCI CTCAE v4.03 was used for the lab parameters. Grade 1: mild; Grade 2: moderate; Grade 3: severe or clinically significant; Grade 4: life-threatening.

Hemoglobin decreased, All grades

Group	Value	95% CI
Tucatinib+Trastuzumab (Cohorts A+B)	42
Tucatinib Post-Crossover (Cohort C)	9

Hemoglobin decreased, Grade 3

Group	Value	95% CI
Tucatinib+Trastuzumab (Cohorts A+B)	3
Tucatinib Post-Crossover (Cohort C)	0

Hemoglobin decreased, Grade 4

Group	Value	95% CI
Tucatinib+Trastuzumab (Cohorts A+B)	0
Tucatinib Post-Crossover (Cohort C)	0

Hemoglobin increased: All grades

Group	Value	95% CI
Tucatinib+Trastuzumab (Cohorts A+B)	3
Tucatinib Post-Crossover (Cohort C)	0

Hemoglobin increased: Grade 3

Group	Value	95% CI
Tucatinib+Trastuzumab (Cohorts A+B)	0
Tucatinib Post-Crossover (Cohort C)	0

Hemoglobin increased: Grade 4

Group	Value	95% CI
Tucatinib+Trastuzumab (Cohorts A+B)	0
Tucatinib Post-Crossover (Cohort C)	0

Leukocytes decreased, All grades

Group	Value	95% CI
Tucatinib+Trastuzumab (Cohorts A+B)	21
Tucatinib Post-Crossover (Cohort C)	5

Leukocytes decreased, Grade 3

Group	Value	95% CI
Tucatinib+Trastuzumab (Cohorts A+B)	0
Tucatinib Post-Crossover (Cohort C)	0

Number of Participants With Treatment-Emergent Laboratory Abnormalities (Chemistry): Interim Analysis Secondary · Up to 49.3 months

The following chemistry laboratory parameters were assessed: Potassium increased; potassium decreased; aspartate aminotransferase increased; creatinine increased; alkaline phosphatase increased; total bilirubin increased. Treatment emergent laboratory abnormalities were defined as abnormalities that were new or worsened on or after receiving the first dose of study treatment and up through 30 days after the last dose of study treatment. NCI CTCAE v5.0 was used for creatinine increased. NCI CTCAE v4.03 was used for the other laboratory parameters. Grade 1: mild; Grade 2: moderate; Grade 3: seve

Potassium increased, Grade 1

Group	Value	95% CI
Tucatinib+Trastuzumab (Cohorts A+B)	5
Tucatinib Pre-Crossover (Cohort C)	1

Potassium increased, Grade 2

Group	Value	95% CI
Tucatinib+Trastuzumab (Cohorts A+B)	1
Tucatinib Pre-Crossover (Cohort C)	0

Potassium increased, Grade 3

Group	Value	95% CI
Tucatinib+Trastuzumab (Cohorts A+B)	0
Tucatinib Pre-Crossover (Cohort C)	1

Potassium increased, Grade 4

Group	Value	95% CI
Tucatinib+Trastuzumab (Cohorts A+B)	0
Tucatinib Pre-Crossover (Cohort C)	0

Potassium decreased, Grade 1

Group	Value	95% CI
Tucatinib+Trastuzumab (Cohorts A+B)	13
Tucatinib Pre-Crossover (Cohort C)	3

Potassium decreased, Grade 2

Group	Value	95% CI
Tucatinib+Trastuzumab (Cohorts A+B)	0
Tucatinib Pre-Crossover (Cohort C)	0

Potassium decreased, Grade 3

Group	Value	95% CI
Tucatinib+Trastuzumab (Cohorts A+B)	1
Tucatinib Pre-Crossover (Cohort C)	1

Potassium decreased, Grade 4

Group	Value	95% CI
Tucatinib+Trastuzumab (Cohorts A+B)	0
Tucatinib Pre-Crossover (Cohort C)	0

Adverse events — posted to ClinicalTrials.gov

Time frame: All-cause mortality: From start of study treatment to death by any cause (maximum up to 71.8 months); adverse events were followed during the safety reporting period (from Day 1 through 30 days after the last dose of study treatment) maximum up to 65.1 months. Reporting threshold: 2%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Tucatinib+Trastuzumab (Cohorts A+B)

Serious: 20/86 (23%)

Deaths: 54/86

Tucatinib Pre-Crossover (Cohort C)

Serious: 3/30 (10%)

Deaths: 2/31

Tucatinib Post-Crossover (Cohort C)

Serious: 6/28 (21%)

Deaths: 15/28

Serious adverse events (38 terms)

Reaction	System	Tucatinib+Trastuzumab (Coh…	Tucatinib Pre-Crossover (C…	Tucatinib Post-Crossover (…
Large intestinal obstruction	Gastrointestinal disorders	—	—	—
Small intestinal obstruction	Gastrointestinal disorders	—	—	—
Urinary tract infection	Infections and infestations	—	—	—
Abdominal pain	Gastrointestinal disorders	—	—	—
Rectal perforation	Gastrointestinal disorders	—	—	—
COVID-19 pneumonia	Infections and infestations	—	—	—
Angina unstable	Cardiac disorders	—	—	—
Cardiac failure	Cardiac disorders	—	—	—
Colitis	Gastrointestinal disorders	—	—	—
Constipation	Gastrointestinal disorders	—	—	—
Dyspepsia	Gastrointestinal disorders	—	—	—
Gastrointestinal obstruction	Gastrointestinal disorders	—	—	—
Nausea	Gastrointestinal disorders	—	—	—
Fatigue	General disorders	—	—	—
Malaise	General disorders	—	—	—
Bile duct stone	Hepatobiliary disorders	—	—	—
Cholangitis	Hepatobiliary disorders	—	—	—
Cholecystitis	Hepatobiliary disorders	—	—	—
Anorectal infection	Infections and infestations	—	—	—
Kidney infection	Infections and infestations	—	—	—
Sepsis	Infections and infestations	—	—	—
Urinary tract infection bacterial	Infections and infestations	—	—	—
Humerus fracture	Injury, poisoning and procedural complications	—	—	—
Radius fracture	Injury, poisoning and procedural complications	—	—	—
Ulna fracture	Injury, poisoning and procedural complications	—	—	—

Other adverse events (148 terms — click to expand)

Reaction	System	Tucatinib+Trastuzumab (Coh…	Tucatinib Pre-Crossover (C…	Tucatinib Post-Crossover (…
Diarrhoea	Gastrointestinal disorders	—	—	—
Fatigue	General disorders	—	—	—
Nausea	Gastrointestinal disorders	—	—	—
Pyrexia	General disorders	—	—	—
Infusion related reaction	Injury, poisoning and procedural complications	—	—	—
Decreased appetite	Metabolism and nutrition disorders	—	—	—
Dermatitis acneiform	Skin and subcutaneous tissue disorders	—	—	—
Chills	General disorders	—	—	—
Arthralgia	Musculoskeletal and connective tissue disorders	—	—	—
Back pain	Musculoskeletal and connective tissue disorders	—	—	—
Cough	Respiratory, thoracic and mediastinal disorders	—	—	—
Hypertension	Vascular disorders	—	—	—
Vomiting	Gastrointestinal disorders	—	—	—
Constipation	Gastrointestinal disorders	—	—	—
Dyspnoea	Respiratory, thoracic and mediastinal disorders	—	—	—
Abdominal pain	Gastrointestinal disorders	—	—	—
Myalgia	Musculoskeletal and connective tissue disorders	—	—	—
Anaemia	Blood and lymphatic system disorders	—	—	—
Headache	Nervous system disorders	—	—	—
Anxiety	Psychiatric disorders	—	—	—
Pruritus	Skin and subcutaneous tissue disorders	—	—	—
Weight decreased	Investigations	—	—	—
Pain in extremity	Musculoskeletal and connective tissue disorders	—	—	—
Nasal congestion	Respiratory, thoracic and mediastinal disorders	—	—	—
Dry skin	Skin and subcutaneous tissue disorders	—	—	—
Influenza like illness	General disorders	—	—	—
Oedema peripheral	General disorders	—	—	—
Dehydration	Metabolism and nutrition disorders	—	—	—
Muscle spasms	Musculoskeletal and connective tissue disorders	—	—	—
Peripheral sensory neuropathy	Nervous system disorders	—	—	—
Insomnia	Psychiatric disorders	—	—	—
Epistaxis	Respiratory, thoracic and mediastinal disorders	—	—	—
Rash maculo-papular	Skin and subcutaneous tissue disorders	—	—	—
Abdominal pain upper	Gastrointestinal disorders	—	—	—
COVID-19	Infections and infestations	—	—	—
Productive cough	Respiratory, thoracic and mediastinal disorders	—	—	—
Upper-airway cough syndrome	Respiratory, thoracic and mediastinal disorders	—	—	—
Asthenia	General disorders	—	—	—
Alanine aminotransferase increased	Investigations	—	—	—
Aspartate aminotransferase increased	Investigations	—	—	—

Most-reported serious reactions: Large intestinal obstruction, Small intestinal obstruction, Urinary tract infection, Abdominal pain, Rectal perforation, COVID-19 pneumonia, Angina unstable, Cardiac failure.

Data from ClinicalTrials.gov NCT03043313 adverse events section.

Sponsor's own description

This trial studies how well the drug tucatinib works when given with trastuzumab and when given by itself. The participants in this trial have HER2-positive (HER2+) metastatic colorectal cancer (mCRC). 'Metastatic' means that the cancer has spread to other parts of the body.

In the first part of this study, participants enrolled into Cohort A and received both tucatinib and trastuzumab. In the second part of this study, participants are randomly assigned to either Cohort B or Cohort C. Participants in Cohort B will receive tucatinib and trastuzumab. Participants in Cohort C will receive tucatinib. Participants in Cohort C who do not respond to therapy may have an option to receive tucatinib plus trastuzumab.

Publications & conference data

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

1. Tucatinib plus trastuzumab for chemotherapy-refractory, HER2-positive, RAS wild-type unresectable or metastatic colorectal cancer (MOUNTAINEER): a multicentre, open-label, phase 2 study.
   Strickler JH, Cercek A, Siena S, André T, et al · · 2023 · cited 168× · PMID 37142372 · DOI 10.1016/s1470-2045(23)00150-x
2. 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
3. Tucatinib and Trastuzumab for Previously Treated Human Epidermal Growth Factor Receptor 2-Positive Metastatic Biliary Tract Cancer (SGNTUC-019): A Phase II Basket Study.
   Nakamura Y, Mizuno N, Sunakawa Y, Canon JL, et al · · 2023 · cited 77× · PMID 37751561 · DOI 10.1200/jco.23.00606
4. Pan-Asian adapted ESMO Clinical Practice Guidelines for the diagnosis, treatment and follow-up of patients with metastatic colorectal cancer.
   Yoshino T, Cervantes A, Bando H, Martinelli E, et al · · 2023 · cited 54× · PMID 37236086 · DOI 10.1016/j.esmoop.2023.101558
5. Monoclonal antibodies and chimeric antigen receptor (CAR) T cells in the treatment of colorectal cancer.
   Jin KT, Chen B, Liu YY, Lan HU, et al · · 2021 · cited 30× · PMID 33522929 · DOI 10.1186/s12935-021-01763-9
6. Colorectal Cancer: From Genetic Landscape to Targeted Therapy.
   El Bali M, Bakkach J, Bennani Mechita M. · · 2021 · cited 29× · PMID 34326875 · DOI 10.1155/2021/9918116
7. Therapeutic Development by Targeting the cGAS-STING Pathway in Autoimmune Disease and Cancer.
   Li Q, Tian S, Liang J, Fan J, et al · · 2021 · cited 27× · PMID 34867409 · DOI 10.3389/fphar.2021.779425
8. Sequential HER2 blockade as effective therapy in chemorefractory, HER2 gene-amplified, RAS wild-type, metastatic colorectal cancer: learning from a clinical case.
   Martinelli E, Troiani T, Sforza V, Martini G, et al · · 2018 · cited 27× · PMID 29387480 · DOI 10.1136/esmoopen-2017-000299