TY - JOUR
T1 - 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
T2 - A meta-analysis of prospective randomized trials
AU - Hasegawa, Yoshikazu
AU - Ando, Masahiko
AU - Maemondo, Makoto
AU - Yamamoto, Satomi
AU - Isa, Shun Ichi
AU - Saka, Hideo
AU - Kubo, Akihito
AU - Kawaguchi, Tomoya
AU - Takada, Minoru
AU - Rosell, Rafael
AU - Kurata, Takayasu
AU - Ignatius Ou, Sai Hong
N1 - Publisher Copyright:
© AlphaMed Press 2015.
PY - 2015/3/1
Y1 - 2015/3/1
N2 - 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 HRwas 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 HRfor 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 HRforexon 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.
AB - 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 HRwas 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 HRfor 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 HRforexon 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.
KW - Afatinib
KW - EGFR TKIs
KW - EGFR mutant non-small cell lung cancer
KW - Erlotinib
KW - Gefitinib
KW - Meta-analysis
KW - Smoking status
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UR - http://www.scopus.com/inward/citedby.url?scp=84925393659&partnerID=8YFLogxK
U2 - 10.1634/theoncologist.2014-0285
DO - 10.1634/theoncologist.2014-0285
M3 - Article
C2 - 25657199
AN - SCOPUS:84925393659
SN - 1083-7159
VL - 20
SP - 307
EP - 315
JO - Oncologist
JF - Oncologist
IS - 3
ER -
