Afatinib in the treatment of EGFR mutation-positive NSCLC - A network meta-analysis
Journal
Lung Cancer
Journal Volume
85
Journal Issue
2
Pages
230-238
Date Issued
2014
Author(s)
Abstract
Objectives: Epidermal growth factor receptor (EGFR) mutation-positive non-small cell lung cancer (NSCLC) is a specific lung cancer subtype characterized by sensitivity to treatment with EGFR tyrosine kinase inhibitors (TKIs). Two reversible EGFR TKIs (gefitinib, erlotinib) and the irreversible ErbB family blocker afatinib are currently approved for treatment of EGFR mutation-positive NSCLC, but no head-to-head trials have been reported to date. We aimed to assess the relative efficacy of the three drugs by conducting a network meta-analysis (NMA). Materials and methods: A systematic literature review was conducted to identify all the available evidence. Outcomes of interest were progression-free survival (PFS) and overall survival. For PFS, results by investigator review were considered as not all trials assessed PFS independently. Results were analyzed using Bayesian methods. Results: The literature search identified 246 articles that were assessed for eligibility, of which 21 studies were included in the NMA, including eight trials performed in an EGFR mutation-positive population. The estimated PFS HR (95% credible interval, CrI) for afatinib compared with gefitinib was 0.70 (0.40-1.16) and compared with erlotinib was 0.86 (0.50-1.50) in the total population. The estimated probability of being best for afatinib over all other treatments for PFS was 70% versus 27% for erlotinib and 3% for gefitinib; the estimated probability of chemotherapy being the best treatment was 0%. Estimated HR (95% CrI) in patients with common mutations was 0.73 (0.42-1.24) for afatinib compared with erlotinib and 0.60 (0.34-0.99) for afatinib compared with gefitinib. OS findings were not significantly different between treatments. Conclusions: In the absence of direct head-to-head trial data comparing efficacy between the three EGFR TKIs, our analysis suggests that afatinib is a viable treatment alternative to erlotinib or gefitinib in terms of PFS. A direct trial-based comparison of the efficacy of these agents is warranted to clarify their relative benefits. ? 2014 Elsevier Ireland Ltd.
Subjects
Afatinib; Chemotherapy; Epidermal growth factor receptor (EGFR); Erlotinib; Gefitinib; NSCLC; Tyrosine kinase inhibitor
SDGs
Other Subjects
afatinib; epidermal growth factor receptor; erlotinib; gefitinib; afatinib; antineoplastic agent; epidermal growth factor receptor; protein kinase inhibitor; quinazoline derivative; article; cancer chemotherapy; cancer survival; comparative effectiveness; drug efficacy; gene mutation; human; lung non small cell cancer; meta analysis; monotherapy; overall survival; priority journal; progression free survival; sensitivity analysis; systematic review; treatment outcome; Carcinoma, Non-Small-Cell Lung; genetics; Lung Neoplasms; mortality; mutation; pathology; proportional hazards model; Antineoplastic Agents; Carcinoma, Non-Small-Cell Lung; Humans; Lung Neoplasms; Mutation; Proportional Hazards Models; Protein Kinase Inhibitors; Quinazolines; Receptor, Epidermal Growth Factor; Treatment Outcome
Publisher
Elsevier Ireland Ltd
Type
journal article