Bevacizumab Or Standard Chemotherapy In Previously Treated Patients With Metastatic Colorectal Cancer - A Systematic Review

Introduction. The BRAF V600E mutation (BRAFmt) occurring in the metastatic colorectal cancer (mCRC) patients is associated with poorer prognosis, in comparison to the wild-type variant of the BRAF gene (BRAFwt). Aim of this work was to assess the clinical efficacy of bevacizumab (BEVA) or standard chemotherapy (ChT) in the 2nd or further lines of treatment in mCRC BRAFmt population.Material and methods. MEDLINE/PubMed, Embase and Cochrane CENTRAL databases were systematically searched. The reference lists of relevant studies were also checked.Results. 6 eligible trials were identified: MOMA (BEVA +/- ChT), allowing for limited overall survival (OS) assessment, WJOG 6210G (BEVA + FOLFIRI), RAISE and 20050181 (FOLFIRI), PICCOLO and Spindler 2013 (irinotecan monotherapy). None of those trials were designed for the treatment evaluation in BRAFmt population. Available evidence was restricted to limited analyses in small subgroups (from a few to several dozens of patients), occasionally comprising RAS gene mutation (RASmt) as well. Based on the identified studies, the comparison of BEVA +/- ChT vs. ChT or among different ChTs in BRAFmt population was not feasible.In case of BEVA (MOMA), OS hazard ratio (HR) for BRAFmt vs. BRAFwt was 1.52 (95% CI: 0.79-2.89) with difference in medians equal to 12.1 months (19.2 vs. 31.3 months, respectivelly), and BRAFmt or RASmt patients had median OS lower by 7.9 months and median progression free survival (PFS) by 3.0 months in WJOG 6210G trial. In case of ChT, median PFS was lower in BRAFmt by 12-67% (HRs range: 1.01-5.3), and median OS by 34-73% (HRs range: 1.05-5.00).Conclusions. Due to limited clinical evidence, assessment of further lines of treatment in BRAFmt mCRC patients is uncertain, however existing data consistently suggest lower effectiveness of BEVA +/- ChT or ChT in BRAFmt, than in BRAFwt subgroup. Hopefully, combining anti-EGFR therapies with BRAF/MEK inhibitor is expected to improve prognosis of those patients.