The Role of Anti-Angiogenics in Pre-Treated Metastatic <i>BRAF</i>-Mutant Colorectal Cancer: A Pooled Analysis

Abstract

Background. FOLFOXIRI plus Bevacizumab is one of the most frequently used first-line treatments for patients with BRAF-mutant colorectal cancer (CRC), while second-line treatment requires extensive further research. In this pooled analysis, we evaluate the impact of anti-angiogenics in patients with pre-treated BRAF-mutant CRC. Methods. We monitored patients in randomized, controlled studies who had advanced CRC and were undergoing second-line chemotherapy in addition to utilizing Bevacizumab, Ramucirumab or Aflibercept treatments. These data were pooled together with the data and results of BRAF-mutant patients enrolled in two phase III trials (TRIBE and TRIBE-2 study), who had been treated with second-line treatment both with or without Bevacizumab. Overall survival (OS), in relation to BRAF mutational status, was the primary focus. Results. Pooled analysis included 129 patients. Anti-angiogenics were found to have a significant advantage over the placebo in terms of OS (HR 0.50, 95%CI 0.29–0.85) (p = 0.01). Conclusions. Our pooled analysis confirms the efficacy of anti-angiogenics in pre-treated BRAF-mutant CRC, establishing the combination of chemotherapy plus Bevacizumab or Ramucirumab or Aflibercept as a valid treatment option.

Keywords

• colorectal cancer
• BRAF mutation
• anti-angiogenics
• chemotherapy
• MSI-H