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- Title
The Role of Smoking Status on the Progression-Free Survival of Non-Small Cell Lung Cancer Patients Harboring Activating Epidermal Growth Factor Receptor (EGFR) Mutations Receiving First-Line EGFR Tyrosine Kinase Inhibitor Versus Platinum Doublet Chemotherapy: A Meta-Analysis of Prospective Randomized Trials
- Authors
Hasegawa, Yoshikazu; Ando, Masahiko; Maemondo, Makoto; Yamamoto, Satomi; Isa, Shun‐ichi; Saka, Hideo; Kubo, Akihito; Kawaguchi, Tomoya; Takada, Minoru; Rosell, Rafael; Kurata, Takayasu; Ou, Sai‐Hong Ignatius
- Abstract
Background. Univariate analyses from several randomized phase III trials seemed to suggest ever-smokers with advanced mutated epidermal growth factor receptor (EGFRm) non-small cell lung cancer (NSCLC) did not seem to benefit from EGFR tyrosine kinase inhibitors (TKIs) as first-line treatment when compared with platinum-doublet chemotherapy as measured by progression-free survival (PFS). Methods. Aliterature-basedmeta-analysis of PFS outcomesas measured by log-transformed pooled hazard ratio (HR) was performed using a random-effect model. Pooled HRs for smoking status, age, gender, ethnicity, type of EGFR mutation, andEGFRTKIwereobtained. Comparison of the pooledHRwas performed by metaregression analysis. Results. Among the 1,649 EGFRm NSCLC patients analyzed from 7 prospective randomized trials (WJTOG3405, NEJ002, EURTAC, OPTIMAL, LUX Lung-3, LUX Lung-6, and ENSURE), 83.7% were Asians, and 30.0% were ever-smokers. An equal percentage of ever-smokers received doublet chemotherapy (30.2%) or EGFR TKI (30.0%). The pooled HR for PFS was 0.29 (95% confidence interval [CI]: 0.21-0.39) for never-smokers and 0.54 (95% CI: 0.38-0.76) for ever-smokers (p , .007 by metaregression).The pooled PFS HR for exon 19 deletionwas 0.25 (95% CI: 0.19-0.31) and 0.44 for exon 21 substitution (95% CI: 0.34-0.57) (p , .001 by metaregression analysis). The pooled PFS HR was 0.33 (95% CI: 0.24-0.46) for Asians and 0.48 for non-Asians (95% CI: 0.28-0.84) (p 5 .261 by metaregression analysis). Conclusion. EGFRm NSCLC patients derived significant PFS benefit from TKI over platinum-doublet chemotherapy as firstline treatment regardless of smoking status; however, PFS benefit is significantly better in never-smokers by metaregression analysis.
- Subjects
LUNG cancer &; genetics; PLATINUM compounds; PROTEIN kinase inhibitors; CANCER chemotherapy; CELL receptors; CONFIDENCE intervals; EPIDERMAL growth factor; LUNG cancer; MEDLINE; META-analysis; GENETIC mutation; ONLINE information services; SMOKING; SURVIVAL; SYSTEMATIC reviews; DATA analysis software; DESCRIPTIVE statistics; THERAPEUTICS
- Publication
Oncologist, 2015, Vol 20, Issue 3, p307
- ISSN
1083-7159
- Publication type
Article
- DOI
10.1634/theoncologist.2014-0285