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J Clin Oncol. 2015 Jun 10;33(17):1958-65. doi: 10.1200/JCO.2014.58.1736. Epub 2015 Apr 20.

Impact of Specific Epidermal Growth Factor Receptor (EGFR) Mutations and Clinical Characteristics on Outcomes After Treatment With EGFR Tyrosine Kinase Inhibitors Versus Chemotherapy in EGFR-Mutant Lung Cancer: A Meta-Analysis.

Author information

1
Chee Khoon Lee, Pei Ni Ding, Sarah J. Lord, and Val Gebski, National Health and Medical Research Council Clinical Trials Centre, The University of Sydney; Chee Khoon Lee and Matthew Links, Cancer Care Centre, St George Hospital; Pei Ni Ding, Liverpool Hospital; Sarah J. Lord, School of Medicine, The University of Notre Dame; Nick Pavlakis, Royal North Shore Hospital, Sydney, Australia; Yi-Long Wu, Guangdong Lung Cancer Institute, Guangdong General Hospital and Guangdong Academy of Medical Sciences, Guangdong; Caicun Zhou, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China; Akira Inoue, Tohoku University Hospital, Sendai; Tetsuya Mitsudomi, Kinki University School of Medicine, Osaka-Sayama, Japan; Rafael Rosell, Catalan Institute of Oncology, Germans Trias i Pujol Health Sciences Institute and Hospital, Barcelona, Spain; Richard J. Gralla, Albert Einstein College of Medicine, Jacobi Medical Center, Bronx, NY; James Chih-Hsin Yang, Graduate Institute of Oncology, National Taiwan University, and National Taiwan University Hospital, Taipei, Taiwan.
2
Chee Khoon Lee, Pei Ni Ding, Sarah J. Lord, and Val Gebski, National Health and Medical Research Council Clinical Trials Centre, The University of Sydney; Chee Khoon Lee and Matthew Links, Cancer Care Centre, St George Hospital; Pei Ni Ding, Liverpool Hospital; Sarah J. Lord, School of Medicine, The University of Notre Dame; Nick Pavlakis, Royal North Shore Hospital, Sydney, Australia; Yi-Long Wu, Guangdong Lung Cancer Institute, Guangdong General Hospital and Guangdong Academy of Medical Sciences, Guangdong; Caicun Zhou, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China; Akira Inoue, Tohoku University Hospital, Sendai; Tetsuya Mitsudomi, Kinki University School of Medicine, Osaka-Sayama, Japan; Rafael Rosell, Catalan Institute of Oncology, Germans Trias i Pujol Health Sciences Institute and Hospital, Barcelona, Spain; Richard J. Gralla, Albert Einstein College of Medicine, Jacobi Medical Center, Bronx, NY; James Chih-Hsin Yang, Graduate Institute of Oncology, National Taiwan University, and National Taiwan University Hospital, Taipei, Taiwan. chihyang@ntu.edu.tw.

Abstract

PURPOSE:

We examined the impact of different epidermal growth factor receptor (EGFR) mutations and clinical characteristics on progression-free survival (PFS) in patients with advanced EGFR-mutated non-small-cell lung cancer treated with EGFR tyrosine kinase inhibitors (TKIs) as first-line therapy.

PATIENTS AND METHODS:

This meta-analysis included randomized trials comparing EGFR TKIs with chemotherapy. We calculated hazard ratios (HRs) and 95% CIs for PFS for the trial population and prespecified subgroups and calculated pooled estimates of treatment efficacy using the fixed-effects inverse-variance-weighted method. All statistical tests were two sided.

RESULTS:

In seven eligible trials (1,649 patients), EGFR TKIs, compared with chemotherapy, significantly prolonged PFS overall (HR, 0.37; 95% CI, 0.32 to 0.42) and in all subgroups. For tumors with exon 19 deletions, the benefit was 50% greater (HR, 0.24; 95% CI, 0.20 to 0.29) than for tumors with exon 21 L858R substitution (HR, 0.48; 95% CI, 0.39 to 0.58; Pinteraction < .001). Never-smokers had a 36% greater benefit (HR, 0.32; 95% CI, 0.27 to 0.37) than current or former smokers (HR, 0.50; 95% CI, 0.40 to 0.63; Pinteraction < .001). Women had a 27% greater benefit (HR, 0.33; 95% CI, 0.28 to 0.38) than men (HR, 0.45; 95% CI, 0.36 to 0.55; treatment-sex interaction P = .02). Performance status, age, ethnicity, and tumor histology did not significantly predict additional benefit from EGFR TKIs.

CONCLUSION:

Although EGFR TKIs significantly prolonged PFS overall and in all subgroups, compared with chemotherapy, greater benefits were observed in those with exon 19 deletions, never-smokers, and women. These findings should enhance drug development and economic analyses, as well as the design and interpretation of clinical trials.

PMID:
25897154
DOI:
10.1200/JCO.2014.58.1736
[Indexed for MEDLINE]

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