Efficacy and Safety of Second-Line FOLFIRI Plus Ramucirumab According to Prior First-Line Regimens in Metastatic Colorectal Cancer: A Multicenter Retrospective Study

Background: Fluorouracil, leucovorin, and irinotecan (FOLFIRI) plus ramucirumab is a well-established second-line treatment for metastatic colorectal cancer (mCRC) following bevacizumab-based chemotherapy. However, its efficacy after other first-line regimens, including anti-EGFR antibody-based and triplet chemotherapy, remains insufficiently characterized. The aim of this study was to compare the efficacy and safety of FOLFIRI plus ramucirumab between patients treated with different first-line treatment regimens. Methods: This retrospective multicenter study included 186 mCRC patients who received second-line FOLFIRI plus ramucirumab between 2016 and 2025. Patients were classified into three groups based on their first-line regimens: Bmab (bevacizumab-based), EGFR (anti-EGFR antibody-based), and Triplet (triplet chemotherapy). The primary endpoint was progression-free survival (PFS). Survival outcomes were evaluated using the Kaplan–Meier method and a propensity score-stratified Cox proportional hazards model. Results: The incidence of grade ≥ 3 adverse events, the median PFS and overall survival (OS) in the Bmab, EGFR, and Triplet groups were comparable (adverse events; 33.8%, 33.3%, 37.3%; PFS: 8.2, 8.6, and 8.7 months; and OS: 18.9, 23.0, and 17.8 months, respectively). In the propensity score-adjusted model using the Bmab group as the reference, there were no differences in PFS (adjusted hazard ratio [95% CI]: 1.84 [0.88–3.83] and 0.97 [0.66–1.45] in the EGFR and Triplet groups, respectively) or OS (1.26 [0.64–2.47] and 0.84 [0.55–1.29] in the EGFR and Triplet groups, respectively). Conclusions: FOLFIRI plus ramucirumab showed consistent efficacy and manageable safety across different prior first-line regimens in real-world practice. Hence, it is a viable option even after anti-EGFR antibody-based or triplet chemotherapy.