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Meta-Analysis
. 2014 Jun;9(6):805-11.
doi: 10.1097/JTO.0000000000000156.

Meta-analysis of first-line therapies in advanced non-small-cell lung cancer harboring EGFR-activating mutations

Benjamin Haaland  1 , Pui San Tan, Gilberto de Castro Jr, Gilberto Lopes
Affiliations
Free PMC article
Meta-Analysis

Meta-analysis of first-line therapies in advanced non-small-cell lung cancer harboring EGFR-activating mutations

Benjamin Haaland et al. J Thorac Oncol. 2014 Jun.
Free PMC article

Abstract

Introduction: Tyrosine kinase inhibitors gefitinib, erlotinib, and afatinib have been compared with chemotherapy as first-line therapies for patients with advanced non-small-cell lung cancer harboring epidermal growth factor receptor-activating mutations. This meta-analysis compares gefitinib, erlotinib, afatinib, and chemotherapy.

Methods: Literature search was performed using relevant keywords. Direct and indirect meta-estimates were generated using log-linear mixed-effects models, with random effects for study. Study-to-study heterogeneity was summarized using I statistics and predictive intervals (PIs).

Results: Literature search yielded eight randomized phase 3 clinical trials comparing gefitinib, erlotinib, or afatinib with chemotherapy as first-line therapy in patients with advanced non-small-cell lung cancer during the last 5 years. Hazard ratio meta-estimates for progression-free survival were for gefitinib versus chemotherapy 0.44 (95% confidence interval [CI] 0.31-0.63; 95% PI, 0.22-0.88), erlotinib versus chemotherapy 0.25 (95% CI, 0.15-0.42; 95% PI, 0.11-0.55), afatinib versus chemotherapy 0.44 (95% CI, 0.26-0.75; 95% PI, 0.20-0.98), erlotinib versus gefitinib 0.57 (95% CI, 0.30-1.08; 95% PI, 0.24-1.36), afatinib versus gefitinib 1.01 (95% CI, 0.53-1.92; 95% PI, 0.41-2.42), and erlotinib versus afatinib 0.56 (95% CI, 0.27-1.18; 95% PI, 0.22-1.46). Results for overall response rate and disease control rate were similar. There was no evidence that gefitinib, erlotinib, or afatinib improved overall survival compared with chemotherapy.

Conclusion: Gefitinib, erlotinib, and afatinib out-performed chemotherapy in terms of progression-free survival, overall response rate, and disease control rate. Differences among gefitinib, erlotinib, and afatinib were not statistically significant.

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Conflict of interest statement

Disclosure: Dr. de Castro has received honoraria from Astra Zeneca, Boehringer Ingelheim, and Roche. Dr. Lopes has received honoraria and research funds from Astra Zeneca, Eli Lilly, Roche, and Sanofi. The remaining authors declare no conflict of interest.

Figures

FIGURE 1.
FIGURE 1.
Selection diagram for studies comparing gefitinib, erlotinib, and afatinib with chemotherapy as first-line therapies for patients with advanced NSCLC harboring EGFR-activating mutations. ASCO, American Society of Clinical Oncology; NSCLC, non–small-cell lung cancer; EGFR, epidermal growth factor receptor.
FIGURE 2.
FIGURE 2.
Individual study hazard ratios along with comparative meta-estimates for progression-free survival in first-line therapy for patients with advanced NSCLC harboring EGFR-activating mutations. 95% confidence intervals shown in black and 95% predictive intervals in red. NSCLC, non–small-cell lung cancer.
FIGURE 3.
FIGURE 3.
Individual study odds ratios along with comparative meta-estimates for overall response rate in first-line therapy for patients with advanced NSCLC harboring EGFR-activating mutations. 95% confidence intervals shown in black and 95% predictive intervals in red. NSCLC, non–small-cell lung cancer.
FIGURE 4.
FIGURE 4.
Individual study odds ratios along with comparative meta-estimates for disease control rate in first-line therapy for patients with advanced NSCLC harboring EGFR-activating mutations. 95% confidence intervals shown in black and 95% predictive intervals in red. NSCLC, non–small-cell lung cancer.
See this image and copyright information in PMC

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