Erlotinib in combination with bevacizumab has potential benefit in non-small cell lung cancer: A systematic review and meta-analysis of randomized clinical trials

Lung Cancer. 2018 Aug:122:10-21. doi: 10.1016/j.lungcan.2018.05.011. Epub 2018 May 18.


Objectives: A role for erlotinib and bevacizumab as single agents has been established in the treatment of non-small cell lung cancer (NSCLC). However, the efficacy and safety of erlotinib in combination with bevacizumab compared with single agents remain unclear. This meta-analysis aimed to investigate the status of this combined strategy in NSCLC.

Materials and methods: We systematically searched relevant databases for randomized controlled trials (RCTs) on the use of erlotinib plus bevacizumab in NSCLC. The main outcomes analysis reported overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and adverse effects. Random-effects models were used to estimate pooled hazard ratio and relative risk.

Results: Ten studies with a total of 2802 participants were eligible for meta-analysis, the results of which suggested erlotinib with bevacizumab failed to significantly enhance either OS (95% CI: 0.87-1.12; P = 0.825) or ORR (95% CI: 0.69-1.67; P = 0.758). Though PFS was modestly improved, there was no statistical significance (5.55 months vs. 4.67 months, 95% CI: 0.63-1.15; P = 0.297). Incidence of rash or diarrhea was higher in the combination group than in the single-agent group. Subgroup analysis showed encouraging OS (95% CI: 0.29-0.69; P < 0.001) in epidermal growth factor receptor (EGFR)-mutant patients treated with combination therapy, no such benefits were found in groups restricting on KRAS status.

Conclusion: Erlotinib plus bevacizumab enhances OS for EGFR-mutant patients, with rash and diarrhea common but acceptable adverse effects. Combination treatment can be recommended as the preferable option for EGFR-mutant patients. Further large-scale, well-designed RCTs are required to confirm our validation.

Keywords: Bevacizumab; Erlotinib; Meta-analysis; Non-small cell lung cancer; Targeted therapy.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Systematic Review

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Bevacizumab / therapeutic use*
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / mortality
  • ErbB Receptors / genetics
  • Erlotinib Hydrochloride / therapeutic use*
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / mortality
  • Mutation / genetics
  • Randomized Controlled Trials as Topic
  • Survival Analysis
  • Treatment Outcome


  • Bevacizumab
  • Erlotinib Hydrochloride
  • EGFR protein, human
  • ErbB Receptors