Gefitinib or Erlotinib vs Chemotherapy for EGFR Mutation-Positive Lung Cancer

Individual Patient Data Meta-Analysis of Overall Survival

Chee Khoon Lee, Lucy Davies, Yi Long Wu, Tetsuya Mitsudomi, Akira Inoue, Rafael Rosell, Caicun Zhou, Kazuhiko Nakagawa, Sumitra Thongprasert, Masahiro Fukuoka, Sally Lord, Ian Marschner, Yu Kang Tu, Richard J. Gralla, Val Gebski, Tony Mok, James Chih Hsin Yang

Research output: Contribution to journalArticle

47 Citations (Scopus)

Abstract

Background: We performed an individual patient data meta-analysis to examine the impact of first-generation epidermal growth factor receptor ( EGFR ) tyrosine kinase inhibitor (TKI) therapy on overall survival (OS) in advanced non-small cell lung cancer (NSCLC).

Methods: Data from trials comparing EGFR-TKI against chemotherapy in exon 19 deletion (del19) or exon 21 L858R (L858R) EGFR mutations patients were used. We performed Cox regression to obtain hazard ratios (HRs) and 95% confidence intervals (CIs). Impact of postprogression therapies was examined in exploratory analyses. All statistical tests were two-sided.

Results: Six eligible trials (gefitinib = 3, erlotinib = 3) included 1231 patients; 632 received EGFR-TKI and 599 received chemotherapy. At a median 35.0 months follow-up, there were 780 deaths and 1004 progressions. There was no difference in OS between EGFR-TKI and chemotherapy (HR = 1.01, 95% CI = 0.88 to 1.17, P =  .84). There was also no difference in OS for Del19 (n = 682, HR = 0.96, 95% CI = 0.79 to 1.16, P =  .68) and L858R (n = 540, HR = 1.06, 95% CI = 0.86 to 1.32, P =  .59) subgroups ( P interaction = .47), or according to smoking status, sex, performance status, age, ethnicity, or histology. However, EGFR-TKI statistically significantly prolonged progression-free survival (PFS) overall (HR = 0.37, 95% CI = 0.32 to 0.42, P <  .001) and in all subgroups. Following progression, 73.8% from the chemotherapy arm received EGFR-TKI, and 65.9% from the EGFR-TKI arm received chemotherapy. Nine percent from the EGFR-TKI arm received no further treatment vs 0.6% from the chemotherapy arm. Following disease progression, patients randomly assigned to EGFR-TKI had shorter OS than those randomly assigned to chemotherapy (12.8 months, 95% CI = 11.4 to 14.3, vs 19.8 months, 95% CI = 17.6 to 21.7).

Conclusions: Despite statistically significant PFS benefit, there is no relative OS advantage with frontline gefitinib or erlotinib vs chemotherapy in EGFR -mutated NSCLC. This finding is likely due to the high rate of crossover at progression.

Original languageEnglish (US)
JournalJournal of the National Cancer Institute
Volume109
Issue number6
DOIs
StatePublished - Jun 1 2017

Fingerprint

Epidermal Growth Factor Receptor
Meta-Analysis
Lung Neoplasms
Protein-Tyrosine Kinases
Drug Therapy
Mutation
Survival
Confidence Intervals
Non-Small Cell Lung Carcinoma
Disease-Free Survival
Exons
Erlotinib Hydrochloride
gefitinib
Disease Progression
Histology
Therapeutics
Smoking

ASJC Scopus subject areas

  • Medicine(all)
  • Oncology
  • Cancer Research

Cite this

Gefitinib or Erlotinib vs Chemotherapy for EGFR Mutation-Positive Lung Cancer : Individual Patient Data Meta-Analysis of Overall Survival. / Lee, Chee Khoon; Davies, Lucy; Wu, Yi Long; Mitsudomi, Tetsuya; Inoue, Akira; Rosell, Rafael; Zhou, Caicun; Nakagawa, Kazuhiko; Thongprasert, Sumitra; Fukuoka, Masahiro; Lord, Sally; Marschner, Ian; Tu, Yu Kang; Gralla, Richard J.; Gebski, Val; Mok, Tony; Yang, James Chih Hsin.

In: Journal of the National Cancer Institute, Vol. 109, No. 6, 01.06.2017.

Research output: Contribution to journalArticle

Lee, CK, Davies, L, Wu, YL, Mitsudomi, T, Inoue, A, Rosell, R, Zhou, C, Nakagawa, K, Thongprasert, S, Fukuoka, M, Lord, S, Marschner, I, Tu, YK, Gralla, RJ, Gebski, V, Mok, T & Yang, JCH 2017, 'Gefitinib or Erlotinib vs Chemotherapy for EGFR Mutation-Positive Lung Cancer: Individual Patient Data Meta-Analysis of Overall Survival', Journal of the National Cancer Institute, vol. 109, no. 6. https://doi.org/10.1093/jnci/djw279
Lee, Chee Khoon ; Davies, Lucy ; Wu, Yi Long ; Mitsudomi, Tetsuya ; Inoue, Akira ; Rosell, Rafael ; Zhou, Caicun ; Nakagawa, Kazuhiko ; Thongprasert, Sumitra ; Fukuoka, Masahiro ; Lord, Sally ; Marschner, Ian ; Tu, Yu Kang ; Gralla, Richard J. ; Gebski, Val ; Mok, Tony ; Yang, James Chih Hsin. / Gefitinib or Erlotinib vs Chemotherapy for EGFR Mutation-Positive Lung Cancer : Individual Patient Data Meta-Analysis of Overall Survival. In: Journal of the National Cancer Institute. 2017 ; Vol. 109, No. 6.
@article{68a602d305e140b6a63d1e712078de94,
title = "Gefitinib or Erlotinib vs Chemotherapy for EGFR Mutation-Positive Lung Cancer: Individual Patient Data Meta-Analysis of Overall Survival",
abstract = "Background: We performed an individual patient data meta-analysis to examine the impact of first-generation epidermal growth factor receptor ( EGFR ) tyrosine kinase inhibitor (TKI) therapy on overall survival (OS) in advanced non-small cell lung cancer (NSCLC).Methods: Data from trials comparing EGFR-TKI against chemotherapy in exon 19 deletion (del19) or exon 21 L858R (L858R) EGFR mutations patients were used. We performed Cox regression to obtain hazard ratios (HRs) and 95{\%} confidence intervals (CIs). Impact of postprogression therapies was examined in exploratory analyses. All statistical tests were two-sided.Results: Six eligible trials (gefitinib = 3, erlotinib = 3) included 1231 patients; 632 received EGFR-TKI and 599 received chemotherapy. At a median 35.0 months follow-up, there were 780 deaths and 1004 progressions. There was no difference in OS between EGFR-TKI and chemotherapy (HR = 1.01, 95{\%} CI = 0.88 to 1.17, P =  .84). There was also no difference in OS for Del19 (n = 682, HR = 0.96, 95{\%} CI = 0.79 to 1.16, P =  .68) and L858R (n = 540, HR = 1.06, 95{\%} CI = 0.86 to 1.32, P =  .59) subgroups ( P interaction = .47), or according to smoking status, sex, performance status, age, ethnicity, or histology. However, EGFR-TKI statistically significantly prolonged progression-free survival (PFS) overall (HR = 0.37, 95{\%} CI = 0.32 to 0.42, P <  .001) and in all subgroups. Following progression, 73.8{\%} from the chemotherapy arm received EGFR-TKI, and 65.9{\%} from the EGFR-TKI arm received chemotherapy. Nine percent from the EGFR-TKI arm received no further treatment vs 0.6{\%} from the chemotherapy arm. Following disease progression, patients randomly assigned to EGFR-TKI had shorter OS than those randomly assigned to chemotherapy (12.8 months, 95{\%} CI = 11.4 to 14.3, vs 19.8 months, 95{\%} CI = 17.6 to 21.7).Conclusions: Despite statistically significant PFS benefit, there is no relative OS advantage with frontline gefitinib or erlotinib vs chemotherapy in EGFR -mutated NSCLC. This finding is likely due to the high rate of crossover at progression.",
author = "Lee, {Chee Khoon} and Lucy Davies and Wu, {Yi Long} and Tetsuya Mitsudomi and Akira Inoue and Rafael Rosell and Caicun Zhou and Kazuhiko Nakagawa and Sumitra Thongprasert and Masahiro Fukuoka and Sally Lord and Ian Marschner and Tu, {Yu Kang} and Gralla, {Richard J.} and Val Gebski and Tony Mok and Yang, {James Chih Hsin}",
year = "2017",
month = "6",
day = "1",
doi = "10.1093/jnci/djw279",
language = "English (US)",
volume = "109",
journal = "Journal of the National Cancer Institute",
issn = "0027-8874",
publisher = "Oxford University Press",
number = "6",

}

TY - JOUR

T1 - Gefitinib or Erlotinib vs Chemotherapy for EGFR Mutation-Positive Lung Cancer

T2 - Individual Patient Data Meta-Analysis of Overall Survival

AU - Lee, Chee Khoon

AU - Davies, Lucy

AU - Wu, Yi Long

AU - Mitsudomi, Tetsuya

AU - Inoue, Akira

AU - Rosell, Rafael

AU - Zhou, Caicun

AU - Nakagawa, Kazuhiko

AU - Thongprasert, Sumitra

AU - Fukuoka, Masahiro

AU - Lord, Sally

AU - Marschner, Ian

AU - Tu, Yu Kang

AU - Gralla, Richard J.

AU - Gebski, Val

AU - Mok, Tony

AU - Yang, James Chih Hsin

PY - 2017/6/1

Y1 - 2017/6/1

N2 - Background: We performed an individual patient data meta-analysis to examine the impact of first-generation epidermal growth factor receptor ( EGFR ) tyrosine kinase inhibitor (TKI) therapy on overall survival (OS) in advanced non-small cell lung cancer (NSCLC).Methods: Data from trials comparing EGFR-TKI against chemotherapy in exon 19 deletion (del19) or exon 21 L858R (L858R) EGFR mutations patients were used. We performed Cox regression to obtain hazard ratios (HRs) and 95% confidence intervals (CIs). Impact of postprogression therapies was examined in exploratory analyses. All statistical tests were two-sided.Results: Six eligible trials (gefitinib = 3, erlotinib = 3) included 1231 patients; 632 received EGFR-TKI and 599 received chemotherapy. At a median 35.0 months follow-up, there were 780 deaths and 1004 progressions. There was no difference in OS between EGFR-TKI and chemotherapy (HR = 1.01, 95% CI = 0.88 to 1.17, P =  .84). There was also no difference in OS for Del19 (n = 682, HR = 0.96, 95% CI = 0.79 to 1.16, P =  .68) and L858R (n = 540, HR = 1.06, 95% CI = 0.86 to 1.32, P =  .59) subgroups ( P interaction = .47), or according to smoking status, sex, performance status, age, ethnicity, or histology. However, EGFR-TKI statistically significantly prolonged progression-free survival (PFS) overall (HR = 0.37, 95% CI = 0.32 to 0.42, P <  .001) and in all subgroups. Following progression, 73.8% from the chemotherapy arm received EGFR-TKI, and 65.9% from the EGFR-TKI arm received chemotherapy. Nine percent from the EGFR-TKI arm received no further treatment vs 0.6% from the chemotherapy arm. Following disease progression, patients randomly assigned to EGFR-TKI had shorter OS than those randomly assigned to chemotherapy (12.8 months, 95% CI = 11.4 to 14.3, vs 19.8 months, 95% CI = 17.6 to 21.7).Conclusions: Despite statistically significant PFS benefit, there is no relative OS advantage with frontline gefitinib or erlotinib vs chemotherapy in EGFR -mutated NSCLC. This finding is likely due to the high rate of crossover at progression.

AB - Background: We performed an individual patient data meta-analysis to examine the impact of first-generation epidermal growth factor receptor ( EGFR ) tyrosine kinase inhibitor (TKI) therapy on overall survival (OS) in advanced non-small cell lung cancer (NSCLC).Methods: Data from trials comparing EGFR-TKI against chemotherapy in exon 19 deletion (del19) or exon 21 L858R (L858R) EGFR mutations patients were used. We performed Cox regression to obtain hazard ratios (HRs) and 95% confidence intervals (CIs). Impact of postprogression therapies was examined in exploratory analyses. All statistical tests were two-sided.Results: Six eligible trials (gefitinib = 3, erlotinib = 3) included 1231 patients; 632 received EGFR-TKI and 599 received chemotherapy. At a median 35.0 months follow-up, there were 780 deaths and 1004 progressions. There was no difference in OS between EGFR-TKI and chemotherapy (HR = 1.01, 95% CI = 0.88 to 1.17, P =  .84). There was also no difference in OS for Del19 (n = 682, HR = 0.96, 95% CI = 0.79 to 1.16, P =  .68) and L858R (n = 540, HR = 1.06, 95% CI = 0.86 to 1.32, P =  .59) subgroups ( P interaction = .47), or according to smoking status, sex, performance status, age, ethnicity, or histology. However, EGFR-TKI statistically significantly prolonged progression-free survival (PFS) overall (HR = 0.37, 95% CI = 0.32 to 0.42, P <  .001) and in all subgroups. Following progression, 73.8% from the chemotherapy arm received EGFR-TKI, and 65.9% from the EGFR-TKI arm received chemotherapy. Nine percent from the EGFR-TKI arm received no further treatment vs 0.6% from the chemotherapy arm. Following disease progression, patients randomly assigned to EGFR-TKI had shorter OS than those randomly assigned to chemotherapy (12.8 months, 95% CI = 11.4 to 14.3, vs 19.8 months, 95% CI = 17.6 to 21.7).Conclusions: Despite statistically significant PFS benefit, there is no relative OS advantage with frontline gefitinib or erlotinib vs chemotherapy in EGFR -mutated NSCLC. This finding is likely due to the high rate of crossover at progression.

UR - http://www.scopus.com/inward/record.url?scp=85027265241&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85027265241&partnerID=8YFLogxK

U2 - 10.1093/jnci/djw279

DO - 10.1093/jnci/djw279

M3 - Article

VL - 109

JO - Journal of the National Cancer Institute

JF - Journal of the National Cancer Institute

SN - 0027-8874

IS - 6

ER -