Different doses of bevacizumab in combination with chemotherapy for advanced colorectal cancer: a meta-analysis and Bayesian analysis.

Abstract

The aim of the present study was to explore the incremental benefit of bevacizumab (Bev) in the treatment of advanced colorectal cancer (CRC) with different doses. A literature search of eight electronic databases (China National Knowledge Infrastructure, Wanfang databases, Chinese Biomedical Database, VIP medicine information, Cochrane Library, MEDLINE, PubMed, and EMBASE) was conducted from database creation to December 2022. Randomized controlled trials (RCTs) that compared Bev at various dosages + chemotherapy (CT) versus placebo (or blank control) + CT were selected. The overall survival (OS), progression-free survival (PFS), overall response rate (ORR; complete response [CR] + partial response [PR]), and grade ≥ 3 adverse events (AEs) were integrated first by pooled analysis. The likelihood of ideal dosage of Bev was then ranked using random effects within Bayesian analysis. Twenty-six RCTs involving 18,261 patients met the inclusion criteria. OS increased significantly after using 5mg (HR: 0.87, 95% CI 0.75 to 1.00) and 10mg dosages of Bev (HR: 0.75, 95% CI 0.66 to 0.85) with CT, but statistical significance was not attained for the 7.5mg dose (HR: 0.95, 95% CI 0.83 to 1.08). A significantly increased in PFS with doses of 5mg (HR: 0.69, 95% CI 0.58 to 0.83), 7.5mg (HR: 0.81, 95% CI 0.66 to 1.00), and 10mg (HR: 0.60, 95% CI 0.53 to 0.68). ORR distinctly increased after 5mg (RR: 1.34, 95% CI 1.15 to 1.55), 7.5mg (RR: 1.25, 95% CI 1.05 to 1.50), and10mg (RR: 2.27, 95% CI 1.82 to 2.84) doses were administered. Grade ≥ 3 AEs increased clearly in 5mg (RR: 1.11, 95% CI 1.04 to 1.20) compared to 7.5mg (RR: 1.05, 95% CI 0.82 to 1.35) and 10mg (RR: 1.15, 95% CI 0.98 to 1.36). Bayesian analysis demonstrated that 10mg Bev obtained the maximum time of OS (HR: 0.75, 95% CrI 0.58 to 0.97; probability rank = 0.05) indirectly compared to 5mg and 7.5mg Bev. Compared with 5mg and 7.5mg Bev, 10mg Bev also holds the longest duration for PFS (HR: 0.59, 95% CrI 0.43 to 0.82; probability rank = 0.00). In terms of ORR, 10mg Bev holds the maximum frequency (RR: 2.02, 95% CrI 1.52 to 2.66; probability rank = 0.98) in comparison to 5mg and 7.5mg Bev clearly. For grade ≥ 3 AEs, 10mg Bev has the maximum incidence (RR: 1.15, 95% CrI 0.95 to 1.40, probability rank = 0.67) in comparison to other doses of Bev. The study suggests that 10mg dose Bev could be more effective in treating advanced CRC in efficacy, but 5mg Bev could be more safer in terms of safety.