Survival outcomes of ERBB2-amplified metastatic colorectal cancer treated with first-line chemotherapy

Journal article

Background

HER2-positive or ERBB2 amplified (ERBB2 amp+) metastatic colorectal cancer (mCRC) is an important subgroup due to emerging HER2-targeted therapies. Although ERBB2 amplification is associated with anti-EGFR antibody resistance, optimal first-line treatment remains unclear.

Methods

We analysed data from the Flatiron Health-Foundation Medicine CRC clinico-genomic database, including patients with stage IV or recurrent mCRC diagnosed between January 2012 and March 2022 who underwent tissue-based comprehensive genomic profiling. ERBB2 amp+ was defined as an ERBB2 copy number ≥+3 of the tumour base ploidy.

Results

Among 5545 patients, 144 (3.1%) had ERBB2 amp+ mCRC. These patients showed significantly worse real-world progression-free survival (rwPFS) than ERBB2 amp- patients (median 7.6 vs. 8.7 months; hazard ratio [HR]: 1.20, 95% confidence interval [CI]: 1.01-1.43, p = 0.04). This trend persisted in patients with left-sided RAS/BRAF V600E wild-type and non-MSI-H mCRC treated with chemotherapy plus anti-EGFR antibody (median 8.7 vs. 12.5 months; HR: 2.18, p = 0.02; adjusted HR: 2.33, p = 0.046) or chemotherapy plus bevacizumab (median 8.9 vs. 10.5 months; HR: 1.65, p = 0.04; adjusted HR: 1.75, p = 0.04). Real-world overall survival did not differ significantly.

Conclusion

ERBB2 amp+ mCRC is a small but clinically relevant subgroup with inferior rwPFS across current first-line treatments, highlighting the need for better strategies.

Authors: Matsubara, Y; Bando, H; Nakamura, Y; Misumi, T; Ng, D

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Springer Nature [academic journals on nature.com]
• Journal: British Journal of Cancer
• Publication date: 2025-12-08
• DOI: 10.1038/s41416-025-03270-4
• EISSN: 1532-1827
• ISSN: 0007-0920
• Language: English