A meta-analysis of randomized controlled trials comparing chemotherapy plus bevacizumab with chemotherapy alone in metastatic colorectal cancer

Bevacizumab has demonstrated survival benefit in metastatic colorectal cancer (mCRC) patients when combined with chemotherapy. Several randomized clinical studies have evaluated bevacizumab in combination with chemotherapy. Meta-analysis was performed to better assess the efficacy and safety of bevacizumab with chemotherapy for mCRC. Five clinical trials randomizing a total of 3,103 mCRC patients to chemotherapy alone or to the combined treatment of chemotherapy plus bevacizumab were identified. The efficacy data included progression-free survival (PFS), overall survival (OS), and overall response rate (ORR), and the safety data contained the 60-day all-cause mortality rate, adverse events (AEs), and specific toxicity such as hypertension, thrombosis, bleeding, proteinuria, gastrointestinal perforation, diarrhea, and leucopenia. There was a significant PFS benefit (P = 0.00; hazards ratio [HR] = 0.66) and OS benefit (P = 0.00; HR = 0.77) in favor of the combined treatment. The ORR was significantly higher on the bevacizumab-containing arm (P = 0.021; relative risk [RR] = 1.5), while CR was comparable between the two arms (P = 0.09). A higher incidence of grade 3/4 AEs, grade 3/4 hypertension, grade 3/4 thromboembolic/thrombotic events, grade 3/4 bleeding, and gastrointestinal perforation was associated with the bevacizumab group. The two treatment groups were similar in terms of grade 3/4 proteinuria, grade 3/4 leukopenia, grade 3/4 diarrhea, and the 60-day all-cause mortality rate. The addition of bevacizumab to chemotherapy confers a clinically meaningful and statistically significant improvement in OS, PFS, and ORR. Its side effects are predictable and manageable and do not compound the incidence or severity of toxicities from chemotherapy.