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

Chee Khoon Lee, Yi Long Wu, Pei Ni Ding, Sarah J. Lord, Akira Inoue, Caicun Zhou, Tetsuya Mitsudomi, Rafael Rosell, Nick Pavlakis, Matthew Links, Val Gebski, Richard J. Gralla, James Chih Hsin Yang

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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; P<inf>interaction</inf> < .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; P<inf>interaction</inf> < .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.

Original languageEnglish (US)
Pages (from-to)1958-1965
Number of pages8
JournalJournal of Clinical Oncology
Volume33
Issue number17
DOIs
StatePublished - Jun 10 2015

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Epidermal Growth Factor Receptor
Protein-Tyrosine Kinases
Meta-Analysis
Lung Neoplasms
Drug Therapy
Mutation
Disease-Free Survival
Exons
Neoplasms
Economic Development
Non-Small Cell Lung Carcinoma
Histology
Clinical Trials
Therapeutics
Pharmaceutical Preparations
Population

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

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. / Lee, Chee Khoon; Wu, Yi Long; Ding, Pei Ni; Lord, Sarah J.; Inoue, Akira; Zhou, Caicun; Mitsudomi, Tetsuya; Rosell, Rafael; Pavlakis, Nick; Links, Matthew; Gebski, Val; Gralla, Richard J.; Yang, James Chih Hsin.

In: Journal of Clinical Oncology, Vol. 33, No. 17, 10.06.2015, p. 1958-1965.

Research output: Contribution to journalArticle

Lee, Chee Khoon ; Wu, Yi Long ; Ding, Pei Ni ; Lord, Sarah J. ; Inoue, Akira ; Zhou, Caicun ; Mitsudomi, Tetsuya ; Rosell, Rafael ; Pavlakis, Nick ; Links, Matthew ; Gebski, Val ; Gralla, Richard J. ; Yang, James Chih Hsin. / 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. In: Journal of Clinical Oncology. 2015 ; Vol. 33, No. 17. pp. 1958-1965.
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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.",
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T1 - 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

T2 - A meta-analysis

AU - Lee, Chee Khoon

AU - Wu, Yi Long

AU - Ding, Pei Ni

AU - Lord, Sarah J.

AU - Inoue, Akira

AU - Zhou, Caicun

AU - Mitsudomi, Tetsuya

AU - Rosell, Rafael

AU - Pavlakis, Nick

AU - Links, Matthew

AU - Gebski, Val

AU - Gralla, Richard J.

AU - Yang, James Chih Hsin

PY - 2015/6/10

Y1 - 2015/6/10

N2 - 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.

AB - 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.

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