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Oncologist. 2015 Mar;20(3):307-15. doi: 10.1634/theoncologist.2014-0285. Epub 2015 Feb 5.

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.

Author information

1
Izumi Municipal Hospital, Osaka, Japan; Nagoya University Hospital, Nagoya, Aichi, Japan; Miyagi Cancer Center, Miyagi, Japan; University of Kansas Cancer Center, Kansas City, Kansas, USA; National Hospital Organization Kinki-Chuo Chest Medical Center, Osaka, Japan; National Hospital Organization Nagoya Medical Center, Aichi, Japan; Aichi Medical University School of Medicine, Nagoya, Aichi, Japan; Graduate School of Medicine, Osaka City University, Osaka, Japan; Koyo Hospital, Wakayama, Japan; Catalan Institute of Oncology, Barcelona, Spain; Kansai Medical University Hirakata Hospital, Osaka, Japan; Chao Family Comprehensive Cancer Center, University of California Irvine School of Medicine, Orange, California, USA.
2
Izumi Municipal Hospital, Osaka, Japan; Nagoya University Hospital, Nagoya, Aichi, Japan; Miyagi Cancer Center, Miyagi, Japan; University of Kansas Cancer Center, Kansas City, Kansas, USA; National Hospital Organization Kinki-Chuo Chest Medical Center, Osaka, Japan; National Hospital Organization Nagoya Medical Center, Aichi, Japan; Aichi Medical University School of Medicine, Nagoya, Aichi, Japan; Graduate School of Medicine, Osaka City University, Osaka, Japan; Koyo Hospital, Wakayama, Japan; Catalan Institute of Oncology, Barcelona, Spain; Kansai Medical University Hirakata Hospital, Osaka, Japan; Chao Family Comprehensive Cancer Center, University of California Irvine School of Medicine, Orange, California, USA Ignatius.ou@uci.edu mando@med.nagoya-u.ac.jp.

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:

A literature-based meta-analysis of PFS outcomes as 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, and EGFR TKI were obtained. Comparison of the pooled HR was 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 deletion was 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 = .261 by metaregression analysis).

CONCLUSION:

EGFRm NSCLC patients derived significant PFS benefit from TKI over platinum-doublet chemotherapy as first-line treatment regardless of smoking status; however, PFS benefit is significantly better in never-smokers by metaregression analysis.

KEYWORDS:

Afatinib; EGFR TKIs; EGFR mutant non-small cell lung cancer; Erlotinib; Gefitinib; Meta-analysis; Smoking status

PMID:
25657199
PMCID:
PMC4350797
DOI:
10.1634/theoncologist.2014-0285
[Indexed for MEDLINE]
Free PMC Article

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