Survival outcomes of ERBB2-amplified metastatic colorectal cancer treated with first-line chemotherapy.
Matsubara Y., Bando H., Nakamura Y., Misumi T., Ng D., Tajima E., Pittell H., Ohtsu A., Yoshino T.
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.