Bevacizumab or Aflibercept in Combination with Second-Line FOLFIRI after Progression on FOLFOX Plus Bevacizumab in Metastatic Colorectal Cancer: A Comparative Study.

Abstract

Background: The optimal anti-angiogenic strategy in the second-line treatment of metastatic colorectal cancer (mCRC) after progression on first-line FOLFOX plus bevacizumab remains unclear. We aimed to compare the efficacy and safety of FOLFIRI combined with bevacizumab or aflibercept in this well-defined clinical setting.

Methods: In this retrospective single-center study, 152 patients with mCRC who progressed after at least four cycles of first-line FOLFOX plus bevacizumab were included. Of these, 92 patients received FOLFIRI plus bevacizumab and 60 received FOLFIRI plus aflibercept as second-line therapy. Stabilized inverse probability of treatment weighting (IPTW) was applied to account for baseline differences between treatment groups. PFS and OS were evaluated using IPTW-weighted Kaplan-Meier and Cox regression analyses.

Results: No statistically significant difference was observed between the bevacizumab and aflibercept groups for PFS (HR: 1.302, 95% CI: 0.929-1.825, p=0.125) or OS (HR: 1.212, 95% CI: 0.846-1.736, p=0.295) in the IPTW-weighted analyses. Treatment type was not independently associated with PFS or OS in multivariate analyses. Grade 3-4 toxicities were observed in both groups, with neutropenia being the most common; thrombocytopenia and neutropenia were numerically more frequent in the aflibercept group.

Conclusion: No statistically significant differences in efficacy were observed between FOLFIRI plus bevacizumab and FOLFIRI plus aflibercept in patients with mCRC progressing after first-line FOLFOX plus bevacizumab. Both strategies represent reasonable second-line options in this setting, highlighting the need for prospective studies to define the optimal sequencing of anti-angiogenic therapies.