FOLFIRI plus BEvacizumab or aFLIbercept after FOLFOX-bevacizumab Failure for COlorectal Cancer (BEFLICO): An AGEO Multicenter Study.

Abstract : After failure of first line FOLFOX-bevacizumab for metastatic colorectal cancer (mCRC), adding either bevacizumab or aflibercept to second-line FOLFIRI increases survival compared to FOLFIRI alone. In this French retrospective multicentre cohort, we included patients with a mCRC treated with either FOLFIRI-aflibercept or FOLFIRI-bevacizumab. The primary endpoint was overall survival (OS), and secondary endpoints were progression-free survival (PFS), disease control rate (DCR: CR\,+\,PR\,+\,SD) and safety. We included 681 patients from 36 centers, 326 and 355 in the aflibercept and bevacizumab groups, respectively. Median age was 64.2\,years and 45.2% of patients were men. Most patients had RAS-mutated tumors (80.8%) and synchronous metastases (85.7%). After a median follow up of 31.2~months, median OS was 13.0~months (95% CI: 11.3-14.7) and 10.4~months (95% CI: 8.8-11.4) in the bevacizumab and aflibercept groups, respectively (P\,<\,.0001). Median PFS was 6.0~months (95% CI: 5.4-6.5) and 5.1~months (95% CI: 4.3-5.6) (P\,<\,.0001). After adjustment on age, PS, PFS of first line, primary tumor resection, metastasis location and RAS/BRAF status, bevacizumab was still associated with better OS (HR: 0.71, 95% CI: 0.59-0.86, P~=~.0003). FOLFIRI-bevacizumab combination was associated with longer OS and PFS, and a better tolerability, as compared to FOLFIRI-aflibercept after progression on FOLFOX-bevacizumab.