Efficacy of bevacizumab (Bev) plus chemotherapy (CT) compared to CT alone in previously untreated locally advanced or metastatic non-small cell lung cancer (NSCLC): Systematic review and meta-analysis

ObjectiveTo perform a systematic review and meta-analysis of all randomized controlled trials comparing the efficacy of chemotherapy (CT) plus Bevacizumab (Bev) versus CT alone in previously untreated locally advanced or metastatic non-small cell lung cancer (NSCLC).MethodsSeveral databases were searched, including MEDLINE, EMBASE, LILACS, and CENTRAL. The endpoints were overall survival (OS), progression-free survival (PFS) and side effects. We performed a meta-analysis (MA) of the published data, using a fixed effects model and an additional random effects model, when applicable. The results of the MA are expressed as hazard ratio (HR) or risk ratio (RR), with their corresponding 95% confidence intervals (CI95%). We analyzed the use of Bev in the doses of 7.5 mg/kg and 15 mg/kg.ResultsThe final analysis included 4 trials, comprising 2200 patients. The response rate was higher in patients who received the combination of CT plus Bev 7.5 mg/kg (RR = 0.58; CI95% = 0.46–0.74; p < 0.00001) and Bev 15 mg/kg (RR = 0.53; CI95% = 0.45–0.63; p < 0.00001) with moderate heterogeneity at dose of 15 mg/kg (Chi2 = 4.30, df = 3 (P = 0.23); I2 = 30%). The PFS length was longer in patients who received CT plus Bev 7.5 mg/kg (HR = 0.78, CI95% = 0.68–0.90; p = 0.0005) and Bev 15 mg/kg (HR = 0.72, CI95% = 0.65–0.80; p < 0.00001) with moderate heterogeneity (Bev 7.5 mg/kg: Chi2 = 1.43, df = 1 (P = 0.23); I2 = 30% and Bev 15 mg/kg: Chi2 = 7.43, df = 3 (P = 0.06); I2 = 60%). Differences in these end points remained in favor of CT plus Bev when made the analysis by random-effects model. Overall survival was longer in patients who received CT plus Bev 15 mg/kg (HR = 0.89, CI95% = 0.80–1.00; p = 0.04), with moderate heterogeneity (Chi2 = 5.09, df = 3 (P = 0.17); I2 = 41%). The random-effects model analysis for this endpoint did not confirmed the difference seen in the fixed effects model analysis (HR = 0.90, CI95% = 0.76–1.07; p = 0.23). Severe haematologic toxicities (grade > 3), neutropenia and febrile neutropenia were more common among the patients that received Bev.ConclusionThe combination of CT plus Bev increased the response rate and progression-free survival of patients with NSCLC. With respect to overall survival the benefits of Bev remains uncertain.