Impact of Human Epidermal Growth Factor Receptor 2 in Patients With Metastatic Colorectal Cancer Treated With Chemotherapy Plus Bevacizumab or Anti-EGFRs: Exploratory Analysis of Eight Randomized Trials

作者：Marco Maria Germani, Beatrice Borelli, Tadayoshi Hashimoto, Yoshiaki Nakamura, Simone Oldani, Francesca Battaglin, Francesca Bergamo, Lisa Salvatore, Arndt Stahler, Carlotta Antoniotti, Kohei Shitara, Alan P. Venook, Eiji Oki, Kei Muro, Clara Ugolini, Junpei Soeda, Sara Lonardi, Filippo Pietrantonio, Heinz‐Josef Lenz, Dominik Paul Modest, Takayuki Yoshino, Chiara Cremolini · 发表于：Journal of Clinical Oncology · 年份：2025 · DOI：10.1200/jco-25-01003 · 被引用次数：11 · 研究领域：Colorectal Cancer Treatments and Studies、Genetic factors in colorectal cancer、Gastric Cancer Management and Outcomes

PURPOSE Human epidermal growth factor receptor 2 (HER2) amplification/overexpression (HER2-pos) is detected in 5% of RAS/BRAF wild-type metastatic colorectal cancers (mCRCs). Its prognostic/predictive role in terms of benefit from anti-EGFR/bevacizumab (bev) is debated. Similarly, the role of activating HER2 mutations (mut) is unclear. METHODS We collected individual data of 1,604 patients with proficient mismatch repair (pMMR)/microsatellite stable (MSS) RAS/BRAF wild-type untreated mCRC with HER2 amplification/expression status available enrolled in eight randomized clinical trials (RCT; TRIBE2, TRIPLETE, VALENTINO, ATEZOTRIBE, PANDA, PANAMA, PARADIGM, and CALGB/SWOG80405). Objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) were assessed with respect to HER2 amplification/expression and HER2 mutational status and according to biologics (anti-EGFR/bev). RESULTS Patients with HER2-pos were 81 (5%). HER2-pos patients experienced shorter PFS (median PFS [mPFS]: 9.8 v 12.2 months, hazard ratio [HR], 1.31, P = .02) and OS (median OS [mOS]: 28.0 v 34.9 months, HR, 1.37, P = .01), also after adjustment for covariates ( P adj PFS = .02, P adj OS = .048). ORR was similar between HER2-pos and HER2-negative (HER2-neg) tumors (75% v 72%, odds ratio [OR], 1.21, P = .47). We found no interaction between HER2 amplification/expression status and biologics' effect in terms of PFS ( P int = .76), OS ( P int = .76), and ORR ( P int = .64). In left-sided H...