Overall survival benefits for combining targeted therapy as second-line treatment for advanced non-small-cell-lung cancer: a meta-analysis of published data

PLoS One. 2013;8(2):e55637. doi: 10.1371/journal.pone.0055637. Epub 2013 Feb 8.


Background: Combining targeted therapy has been extensively investigated in previously treated advanced non-small-cell lung cancer (NSCLC), but it is still unclear whether combining targeted therapy might offer any benefits against standard monotherapy with erlotinib. We thus performed a meta-analysis of randomized controlled trials to compare the efficacy and safety of combining targeted therapy versus erlotinib alone as second-line treatment for advanced NSCLC.

Methods: Several databases were searched, including Pubmed, Embase and Cochrane databases. The endpoints were overall survival (OS), progression-free survival (PFS), overall response rate (ORR) and grade 3 or 4 adverse event (AEs). The pooled hazard ratio (HR) or odds ratio (OR), and 95% confidence intervals (CI) were calculated employing fixed- or random-effects models depending on the heterogeneity of the included trials.

Results: Eight eligible trials involved 2417 patients were ultimately identified. The intention to treatment (ITT) analysis demonstrated that combining targeted therapy significantly improved OS (HR 0.90, 95% CI: 0.82-0.99, p = 0.024), PFS (HR 0.83, 95% CI: 0.72-0.97, p = 0.018), and ORR (OR 1.35, 95% CI 1.01-1.80, P = 0.04). Sub-group analysis based on phases of trials, EGFR-status and KRAS status also showed that there was a tendency to improve PFS and OS in combining targeted therapy, except that PFS for patients with EGFR-mutation or wild type KRAS favored erlotinib monotherapy. Additionally, more incidence of grade 3 or 4 rash, fatigue and hypertension were observed in combining targeted therapy.

Conclusions: With the available evidence, combining targeted therapy seems superior over erlotinib monotherapy as second-line treatment for advanced NSCLC. More studies are still needed to identify patients who will most likely benefit from the appropriate combining targeted therapy.

Publication types

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

MeSH terms

  • Carcinoma, Non-Small-Cell Lung / therapy*
  • Humans
  • Lung Neoplasms / therapy*
  • Survival Analysis*

Grant support

The study was supported by grants from the National Natural Science Foundation of China (81001191) and Science and Technology Commission of Shanghai (10PJ1408300). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.