Checkpoint Inhibitors in Metastatic EGFR-Mutated Non-Small Cell Lung Cancer-A Meta-Analysis
Journal
Journal of Thoracic Oncology
Journal Volume
12
Journal Issue
2
Pages
403-407
Date Issued
2017
Author(s)
Abstract
Introduction We performed a meta-analysis to assess the role of immune checkpoint inhibitors as second-line therapy in EGFR-mutant advanced NSCLC. Methods Randomized trials comparing immune checkpoint inhibitors against chemotherapy were identified. We retrieved the hazard ratio (HR) and 95% confidence interval (CI) for overall survival (OS) of the intention-to-treat population and EGFR mutation–defined subgroups. We used the fixed-effects inverse variance–weighted method to pool estimates of treatment efficacy. Statistical tests were two sided. Results In the three included studies that compared immune checkpoint inhibitors (nivolumab [n?= 292], pembrolizumab [n?= 691], and atezolizumab [n?=144]) against docetaxel (n?= 776), immune checkpoint inhibitors significantly prolonged OS over that with docetaxel overall (n?= 1903, HR?= 0.68, 95% CI: 0.61–0.77, p < 0.0001) and in the EGFR wild-type subgroup (n?= 1362, HR?= 0.66, 95% CI: 0.58–0.76, p < 0.0001) but not in the EGFR-mutant subgroup (n?= 186, HR?= 1.05, 95% CI: 0.70–1.55, p < 0.81; treatment-mutation interaction p?= 0.03). Conclusion In EGFR-mutant advanced NSCLC, immune checkpoint inhibitors do not improve OS over that with docetaxel. Mechanisms of acquired resistance to first-line tyrosine kinase inhibitor therapy should be elucidated to guide selection of second-line treatment for these patients. ? 2016 International Association for the Study of Lung Cancer
Subjects
EGFR mutation; Immune checkpoint inhibitors; NSCLC; Predictive biomarker
SDGs
Other Subjects
atezolizumab; docetaxel; epidermal growth factor receptor; nivolumab; pembrolizumab; antineoplastic agent; EGFR protein, human; epidermal growth factor receptor; Article; cancer survival; EGFR gene; gene mutation; human; intention to treat analysis; meta analysis; non small cell lung cancer; overall survival; randomized controlled trial (topic); systematic review; cell cycle checkpoint; drug effects; genetics; immunotherapy; lung tumor; mutation; non small cell lung cancer; pathology; prognosis; secondary; Antineoplastic Agents; Carcinoma, Non-Small-Cell Lung; Cell Cycle Checkpoints; Humans; Immunotherapy; Lung Neoplasms; Mutation; Prognosis; Randomized Controlled Trials as Topic; Receptor, Epidermal Growth Factor
Publisher
Elsevier Inc
Type
journal article