Factors associated with a poor response to gefitinib in the NEJ002 study: Smoking and the L858R mutation

Tatsuro Fukuhara, Makoto Maemondo, Akira Inoue, Kunihiko Kobayashi, Shunichi Sugawara, Satoshi Oizumi, Hiroshi Isobe, Akihiko Gemma, Masao Harada, Hirohisa Yoshizawa, Ichiro Kinoshita, Yuka Fujita, Yasuo Saijo, Koichi Hagiwara, Satoshi Morita, Toshihiro Nukiwa

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Introduction: Epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) treatment is the standard therapy for non-small cell lung cancer (NSCLC) harbouring EGFR-activating mutations. The NEJ002 phase 3 clinical trial demonstrated the efficacy of EGFR-TKI; gefitinib was significantly superior in both progression-free survival (PFS) and objective response rate (ORR) than carboplatin plus paclitaxel. However, several cases showed no response. In this study, we performed further analysis of the characteristics of these non-responders. Methods: Available data from NEJ002 on maximum changes in tumour size were obtained from 103 cases (90.4%) and 110 cases (96.5%) in the carboplatin-paclitaxel and gefitinib groups, respectively. Waterfall plots of maximum tumour size changes were created for non-responders. Results: Five (4.9%) and 9 (8.2%) cases in the carboplatin-paclitaxel and gefitinib groups were non-responders, respectively. The mean pack years of the non-responders in the carboplatin-paclitaxel and gefitinib groups were 0.33 and 31.7, respectively. The ORR of total smokers (61.5%) and heavy smokers (over 40 pack years, 52.6%) in the gefitinib group were significantly lower compared to people who have never smoked (80.0%) (. P=. 0.044 and P=. 0.020, respectively). Smoker cases also showed a tendency towards lower PFS and overall survival (OS). In addition, the EGFR common mutation types did not affect PFS and OS in gefitinib-treated cases in NEJ002. However, in this study, the ORR and waterfall plots showed that gefitinib-treated non-responders who had a deletion in exon 19 in the EGFR gene exhibited a tendency towards a higher response compared to those with a L858R mutation. Conclusions: NSCLC patients with a smoking history or the EGFR L858R mutation may demonstrate a poorer response to gefitinib treatment.

Original languageEnglish
Pages (from-to)181-186
Number of pages6
JournalLung Cancer
Volume88
Issue number2
DOIs
Publication statusPublished - 2015 May 1

Keywords

  • Carboplatin-paclitaxel
  • EGFR
  • Gefitinib
  • L858R mutation
  • NEJ002
  • Smoking

ASJC Scopus subject areas

  • Oncology
  • Pulmonary and Respiratory Medicine
  • Cancer Research

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