Biomarker analyses and final overall survival results from a phase III, randomized, open-label, first-line study of gefitinib versus carboplatin/paclitaxel in clinically selected patients with advanced non - small-cell lung cancer in Asia (IPASS)

Masahiro Fukuoka, Yi Long Wu, Sumitra Thongprasert, Patrapim Sunpaweravong, Swan Swan Leong, Virote Sriuranpong, Tsu Yi Chao, Kazuhiko Nakagawa, Da Tong Chu, Nagahiro Saijo, Emma L. Duffield, Yuri Rukazenkov, Georgina Speake, Haiyi Jiang, Alison A. Armour, Ka Fai To, James Chih Hsin Yang, Tony S K Mok

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Abstract

Purpose: The results of the Iressa Pan-Asia Study (IPASS), which compared gefitinib and carboplatin/paclitaxel in previously untreated never-smokers and light ex-smokers with advanced pulmonary adenocarcinoma were published previously. This report presents overall survival (OS) and efficacy according to epidermal growth factor receptor (EGFR) biomarker status. Patients and Methods: In all, 1,217 patients were randomly assigned. Biomarkers analyzed were EGFR mutation (amplification mutation refractory system; 437 patients evaluable), EGFR gene copy number (fluorescent in situ hybridization; 406 patients evaluable), and EGFR protein expression (immunohistochemistry; 365 patients evaluable). OS analysis was performed at 78% maturity. A Cox proportional hazards model was used to assess biomarker status by randomly assigned treatment interactions for progression-free survival (PFS) and OS. Results: OS (954 deaths) was similar for gefitinib and carboplatin/paclitaxel with no significant difference between treatments overall (hazard ratio [HR], 0.90; 95% CI, 0.79 to 1.02; P = .109) or in EGFR mutation - positive (HR, 1.00; 95% CI, 0.76 to 1.33; P = .990) or EGFR mutation - negative (HR, 1.18; 95% CI, 0.86 to 1.63; P = .309; treatment by EGFR mutation interaction P = .480) subgroups. A high proportion (64.3%) of EGFR mutation - positive patients randomly assigned to carboplatin/paclitaxel received subsequent EGFR tyrosine kinase inhibitors. PFS was significantly longer with gefitinib for patients whose tumors had both high EGFR gene copy number and EGFR mutation (HR, 0.48; 95% CI, 0.34 to 0.67) but significantly shorter when high EGFR gene copy number was not accompanied by EGFR mutation (HR, 3.85; 95% CI, 2.09 to 7.09). Conclusion: EGFR mutations are the strongest predictive biomarker for PFS and tumor response to first-line gefitinib versus carboplatin/paclitaxel. The predictive value of EGFR gene copy number was driven by coexisting EGFR mutation (post hoc analysis). Treatment-related differences observed for PFS in the EGFR mutation - positive subgroup were not apparent for OS. OS results were likely confounded by the high proportion of patients crossing over to the alternative treatment.

Original languageEnglish
Pages (from-to)2866-2874
Number of pages9
JournalJournal of Clinical Oncology
Volume29
Issue number21
DOIs
Publication statusPublished - Jul 20 2011
Externally publishedYes

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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    Fukuoka, M., Wu, Y. L., Thongprasert, S., Sunpaweravong, P., Leong, S. S., Sriuranpong, V., Chao, T. Y., Nakagawa, K., Chu, D. T., Saijo, N., Duffield, E. L., Rukazenkov, Y., Speake, G., Jiang, H., Armour, A. A., To, K. F., Yang, J. C. H., & Mok, T. S. K. (2011). Biomarker analyses and final overall survival results from a phase III, randomized, open-label, first-line study of gefitinib versus carboplatin/paclitaxel in clinically selected patients with advanced non - small-cell lung cancer in Asia (IPASS). Journal of Clinical Oncology, 29(21), 2866-2874. https://doi.org/10.1200/JCO.2010.33.4235