What is the response rate of Amivantanab in metastatic colorectal cancer?

Amivantamab Has No Established Role in Metastatic Colorectal Cancer

Amivantamab is not indicated for metastatic colorectal cancer and has no published efficacy data in this disease. This bispecific EGFR-MET antibody is FDA-approved exclusively for non-small cell lung cancer (NSCLC) with EGFR exon 20 insertions, not for gastrointestinal malignancies 1.

Evidence Base for Amivantamab

The entire clinical development program for amivantamab has focused on NSCLC:

• NSCLC with EGFR Exon 20 Insertions: The CHRYSALIS trial demonstrated a 40% objective response rate with median duration of response of 11.1 months in pretreated NSCLC patients 1
• NSCLC with MET Exon 14 Skipping: Overall response rate of 32% in advanced NSCLC, with 50% response in treatment-naive patients 2
• No colorectal cancer data exists: All published studies and ongoing phase III trials (PAPILLON, MARIPOSA, MARIPOSA-2) exclusively enroll lung cancer patients 1

Standard Treatment for Metastatic Colorectal Cancer

Current evidence-based guidelines for metastatic colorectal cancer do not include amivantamab. The established treatment paradigm includes:

First-Line Therapy Selection Based on Molecular Profile

• MSI-H/dMMR tumors: Pembrolizumab immunotherapy provides superior outcomes compared to chemotherapy 3
• MSS/pMMR, RAS wild-type, left-sided: FOLFOX or FOLFIRI plus anti-EGFR antibody (cetuximab or panitumumab) demonstrates superior overall survival 4, 3
• MSS/pMMR, RAS wild-type, right-sided: FOLFOX or FOLFIRI plus bevacizumab is preferred 3
• RAS-mutant disease: FOLFOX or FOLFIRI plus bevacizumab, as anti-EGFR therapy is ineffective 4, 3

Cytotoxic Backbone Options

• FOLFOX or FOLFIRI: Both regimens have similar activity with different toxicity profiles—more polyneuropathy with oxaliplatin, more diarrhea and alopecia with irinotecan 4
• FOLFOXIRI plus bevacizumab: Reserved for patients requiring high response rates for conversion to resectability 4, 3
• Capecitabine-based regimens: CAPOX is an alternative to FOLFOX with comparable efficacy 4

Critical Distinction: EGFR Biology Differs Between Lung and Colorectal Cancer

The rationale for amivantamab in NSCLC does not translate to colorectal cancer:

• EGFR mutations drive NSCLC: Activating EGFR mutations (exon 19 deletions, L858R, exon 20 insertions) are oncogenic drivers in 10-15% of lung adenocarcinomas 1, 5
• EGFR in colorectal cancer: Wild-type EGFR is overexpressed but not mutated; therapeutic targeting requires monoclonal antibodies (cetuximab, panitumumab) that block ligand binding, not bispecific antibodies targeting mutant receptors 4, 3
• RAS status determines EGFR therapy efficacy in CRC: Anti-EGFR therapy only works in RAS wild-type colorectal cancer, and amivantamab has never been studied in this context 4, 3

Common Pitfall to Avoid

Do not extrapolate lung cancer data to colorectal cancer. Despite both being epithelial malignancies with EGFR expression, the molecular mechanisms, mutation profiles, and therapeutic vulnerabilities are fundamentally different. Using amivantamab off-label in metastatic colorectal cancer would expose patients to significant toxicities (79% rash, 72% infusion reactions) 2, 5 without any evidence of benefit.