Erlotinib-based targeted dual agent versus erlotinib alone in previously treated advanced non-small-cell lung cancer: a meta-analysis of 13 randomized controlled trials

Abstract

Objectives: To compare the effects of an erlotinib-based targeted dual agent with erlotinib alone in previously treated patients with advanced non-small lung cancer (NSCLC).

Patients and methods: The PubMed and Embase databases and the Cochrane Central Register of Controlled Trials were searched for publications between January 2005 and March 2016. Hazard ratios (HRs) with their 95% confidence intervals (CIs), or data for calculating HRs with 95% CIs were derived. Overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and toxicity were assessed.

Results: Thirteen trials with a total of 4509 patients were included in this meta-analysis. Compared with erlotinib alone, combination therapy showed no improvement in OS (HR = 0.95; 95% CI, 0.89–1.02; P = .132) though significantly prolonged PFS (HR = 0.82; 95% CI, 0.75–0.90; P < .001). Combination therapy significantly increased ORR (RR = 1.32; 95% CI, 1.09–1.60; P = .005) and DCR (RR = 1.26; 95% CI, 1.17–1.36, P < .001). Sub-analysis assessment failed to identify any sub-groups which could benefit from combination therapy in terms of OS. Combination therapy was associated with more grade 3 or higher toxic effects (RR = 1.54; 95% CI, 1.22–1.95; P < .001). Patients treated with combination therapy had more grade 3 or greater fatigue (RR = 1.49; 95% CI, 1.16–1.91; P = .002), but did not develop more diarrhea (RR = 2.02; 95% CI, 0.86–4.77; P = .107) or rash (RR = 1.29, 95% CI, 0.90–1.85; P = .172). This study had limitations about heterogeneities among the included trials, and the analysis was not based on individual patient data.

Conclusions: Compared with erlotinib alone, the erlotinib-based targeted dual agent showed a minimal magnitude of improvement in PFS but did not improve OS. The role of erlotinib-based combinations in previously treated patients with NSCLC seemed insignificant.

Keywords:

• Advanced non-small-cell lung cancer
• Efficacy
• Erlotinib
• Meta-analysis
• Targeted therapy

Transparency

Declaration of funding

This study was not funded.

Declaration of financial/other relationships

S.Y., Q.X., Y.Y., X.L., and H.C. have disclosed that they have no significant relationships with or financial interests in any commercial companies related to this study or article.

CMRO peer reviewers on this manuscript have no relevant financial or other relationships to disclose.