Efficacy and Safety of Bevacizumab Plus Oxaliplatin- or Irinotecan-Based Doublet Backbone Chemotherapy as the First-Line Treatment of Metastatic Colorectal Cancer: A Systematic Review and Meta-analysis

Abstract

Introduction and objective: Guidelines recommend combined doublet backbone chemotherapy based on 5-fluorouracil and oxaliplatin (OX) or irinotecan (IR) as the first-line treatment options for metastatic colorectal cancer. However, it is still unknown which is better when combined with bevacizumab (BEV). This systematic review and meta-analysis were performed to compare BEV-IR with BEV-OX regimens in terms of efficacy and safety.

Methods: We searched studies from databases including MEDLINE, EMBASE, CENTRAL, and conference papers. The outcomes were overall response rate, overall survival, progression-free survival, and the incidence of the most common adverse events. The dichotomous data were reported as the risk ratio (RR) and the survival outcomes were extracted as the hazard ratio with 95% confidence interval (CI).

Results: Eleven studies including 5632 patients were identified. No difference was found in overall survival or overall response rate between BEV-IR and BEV-OX regimens. The pooled progression-free survival was significantly longer in the BEV-IR group than the BEV-OX group (hazard ratio = 0.92, 95% CI 0.87-0.98, p = 0.08). Compared with the BEV-OX group, the BEV-IR group was related to a higher risk of bleeding events (RR = 0.80, 95% CI 0.64-0.98, p = 0.03), venous thromboembolism (RR = 0.60, 95% CI 0.46-0.79, p = 0.0002), and diarrhea (RR = 0.71, 95% CI 0.62-0.80, p < 0.00001). Conversely, the BEV-OX group was related to a higher risk of thrombocytopenia (RR 2.39, 95% CI 1.67-3.42, p < 0.00001) and neuropathy (RR 3.80, 95% CI 1.90-7.64, p = 0.0002).

Conclusions: The BEV-IR regimen was superior in improving progression-free survival as the first-line treatment for metastatic colorectal cancer. The two different doublet regimens combined with BEV had their specific features of adverse events.