Survival outcomes of ERBB2-amplified metastatic colorectal cancer treated with first-line chemotherapy
Menée à partir de données portant sur 144 patients atteints d'un cancer colorectal de stade métastatique HER2+ ou avec amplification ERBB2, cette étude évalue l'efficacité, du point de vue de la survie sans progression et de la survie globale, d'une chimiothérapie de première ligne en combinaison avec un anticorps anti-EGFR ou le bévacizumab
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.
British Journal of Cancer , article en libre accès, 2025