The efficacy of additional bevacizumab to cytotoxic chemotherapy regimens for the treatment of colorectal cancer: an updated meta-analysis for randomized trials

Abstract

Background: The addition of bevacizumab (BEV) to cytotoxic chemotherapy regimens (CTX) was believed to be effective; however, its magnitude of benefits is still controversial. So a meta-analysis and systematic review seems to be necessary.

Methods: PubMed and the Cochrane library were systematically searched. All relevant citations comparing CTX with/without BEV were considered for inclusion. Sensitivity and meta-regression analysis were performed to identify potential confounders. All pooled estimates were performed using a random-effects model. All statistical analyses were performed by StataSE 12.0.

Results: The search strategy identified 10 eligible random control trials (RCTs) (n=1366). In our pooled estimates, the additional benefits of BEV to CTX were identified in overall survival (OS) hazard ratio (HR, 0.76; 95% CI, 0.69 to 0.82) and progression-free survival (PFS) (HR, 0.56; 95% CI, 0.51 to 0.60), and prolonged survival duration were also identified for OS (18.2 vs. 16.3, p=0.0003) and PFS (8.9 vs. 6.5, p<0.001). Subgroup analyses stratified by CTX was also performed, evident benefits of additional BEV in OS and PFS can be identified in all subgroups, except for the CTX containing capecitabine in OS. Moreover, the increased rate of incidence was also identified in hypertension, thrombosis, proteinuria, gastrointestinal perforation, and fatigue.

Conclusion: BEV, acting as a targeted agent to CTX, its additional benefit to CTX is at the cost of increased toxicity.

FIG. 1.

Flow chart of included trials.

FIG. 2.

(a) Overall Effect for Overall Survival (OS) (b) Subtotal Effect for OS.

FIG. 3.

(a) Overall Effect for Progression-Free Survival (PFS) (b) Subtotal Effect for PFS.

FIG. 4.

(a) Kaplan-Meier Survival Estimate for OS (b) Kaplan-Meier Survival Estimate for PFS.