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

Lung Cancer. 2011 Oct;74(1):89-97. doi: 10.1016/j.lungcan.2011.01.028. Epub 2011 Mar 5.


Objective: To 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).

Methods: Several 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.

Results: The 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 (Chi(2)=4.30, df=3 (P=0.23); I(2)=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: Chi(2)=1.43, df=1 (P=0.23); I(2)=30% and Bev 15 mg/kg: Chi(2)=7.43, df=3 (P=0.06); I(2)=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 (Chi(2)=5.09, df=3 (P=0.17); I(2)=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.

Conclusion: The 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.

Publication types

  • Comparative Study
  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Antibodies, Monoclonal, Humanized / administration & dosage*
  • Antibodies, Monoclonal, Humanized / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Bevacizumab
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / mortality
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Carcinoma, Non-Small-Cell Lung / physiopathology
  • Chemotherapy, Adjuvant* / adverse effects
  • Disease Progression
  • Disease-Free Survival
  • Drug Dosage Calculations
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / mortality
  • Lung Neoplasms / pathology
  • Lung Neoplasms / physiopathology
  • Neoplasm Metastasis
  • Neoplasm Recurrence, Local
  • Neoplasm Staging
  • Neutropenia / etiology
  • Randomized Controlled Trials as Topic
  • Survival Analysis


  • Antibodies, Monoclonal, Humanized
  • Bevacizumab