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.

Bevacizumab Combined with Chemotherapy Improves Survival for Patients with Metastatic Colorectal Cancer: Evidence from Meta Analysis

“…Reasons for these findings regarding OS might be due to insufficient data available from the ITACa trial [33] at that time, which was acknowledged by the authors [41]. Contrary to this, another meta-analysis [42] found benefit in both OS and PFS when bevacizumab was added to chemotherapy, with the subgroup analysis for OS showing it to be consistent across all chemotherapy regimens except capecitabine.…”

Colon Cancer, Version 1.2017, NCCN Clinical Practice Guidelines in Oncology

“…A recent systematic review with a pooled analysis (29 prospective Several meta-analyses have shown a benefit for the use of bevacizumab in first-line therapy for metastatic CRC. [76][77][78][79][80][81][82][83][84] A meta-analysis of 6 randomized clinical trials (3,060 patients) that assessed the efficacy of bevacizumab in first-line treatment of metastatic CRC found that bevacizumab gave a PFS (HR, 0.72; 95% CI, 0.66-0.78; P<.00001) and OS (HR, 0.84; 95% CI, 0.77-0.91; P<.00001) advantage. 85 However, subgroup analyses showed that the advantage was limited to irinotecan-based regimens.…”

Colon Cancer, Version 3.2014

“…139 Several meta-analyses have shown a benefit for the use of bevacizumab in first-line therapy for metastatic CRC. [140][141][142][143][144] A recent meta-analysis of 6 randomized clinical trials (3060 patients) that assessed the efficacy of bevacizumab in first-line treatment of metastatic CRC found that bevacizumab was associated with a PFS (HR, 0.72; 95% CI, 0.66-0.78; P<.00001) and OS (HR, 0.84; 95% CI, 0.77-0.91; P<.00001) advantage. 145 However, subgroup analyses showed that the advantage was limited to irinotecan-based regimens.…”