Efficacy and safety of bevacizumab in metastatic colorectal cancer: pooled analysis from seven randomized controlled trials

Abstract

Purpose: his analysis pooled individual patient data from randomized controlled trials (RCTs) to more thoroughly examine clinical outcomes when adding bevacizumab to chemotherapy for patients with metastatic colorectal cancer (mCRC).

Patients and methods: Patient data were pooled from the first-line AVF2107, NO16966, ARTIST, AVF0780, AVF2192, and AGITG MAX RCTs and the second-line E3200 RCT. All analyses were based on the intent-to-treat population. To assess differences in time-to-event variables by treatment (chemotherapy with or without placebo vs. chemotherapy plus bevacizumab), stratified random-effects (overall) and fixed-effects (subgroup comparisons) models were used to estimate pooled hazard ratios (HRs) and 95% confidence intervals (CIs).

Results: The analysis population comprised 3,763 patients (1,773 chemotherapy with or without placebo; 1,990 chemotherapy plus bevacizumab). The addition of bevacizumab to chemotherapy was associated with statistically significant increases in overall survival (OS; HR, 0.80; 95% CI, 0.71-0.90) and progression-free survival (PFS; HR, 0.57; 95% CI, 0.46-0.71). The effects on OS and PFS across subgroups defined by chemotherapy backbone (oxaliplatin-based, irinotecan-based), extent of disease (liver metastases only, extensive disease), age (<65, ≥65 years), Eastern Cooperative Oncology Group performance status (0, ≥1), and KRAS status (wild-type, mutant) were consistent with the overall analysis. Incidence rates of grade ≥3 hypertension, proteinuria, bleeding, wound-healing complications, gastrointestinal perforations, and thromboembolic events were increased with bevacizumab treatment.

Conclusion: The use of bevacizumab with chemotherapy resulted in statistically significant increases in OS and PFS for patients with mCRC. The PFS benefit extended across the clinically relevant subgroups examined. The observed safety profile of bevacizumab was consistent with that reported in individual trials.

Keywords: Angiogenesis inhibitors; Antibodies, monoclonal, humanized; Bevacizumab; Colorectal neoplasms.

Figure 1.

Overall survival (OS) in the overall pooled population and in individual studies (first- and second-line trials of bevacizumab). (A): Kaplan-Meier estimate of OS for the overall pooled population. (B): Forest plot of OS by study. Abbreviations: BV, bevacizumab; CI, confidence interval; CT, chemotherapy; HR, hazard ratio; OS, overall survival.

Figure 2.

Progression-free survival (PFS) in the overall pooled population and in individual studies (first- and second-line trials of bevacizumab). (A): Kaplan-Meier estimate of PFS for the pooled population. (B): Forest plot of PFS by study. Abbreviations: BV, bevacizumab; CI, confidence interval; CT, chemotherapy; HR, hazard ratio; PFS, progression-free survival.