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J Clin Oncol. 2017 Dec 20;35(36):4027-4034. doi: 10.1200/JCO.2017.73.9250. Epub 2017 Oct 2.

Gefitinib Plus Chemotherapy Versus Chemotherapy in Epidermal Growth Factor Receptor Mutation-Positive Non-Small-Cell Lung Cancer Resistant to First-Line Gefitinib (IMPRESS): Overall Survival and Biomarker Analyses.

Author information

1
Tony S.K. Mok, The Chinese University of Hong Kong, Prince of Wales Hospital, Sha Tin, Hong Kong, Special Administrative Region, People's Republic of China; Yi-Long Wu and Jin-Ji Yang, Guangdong General Hospital and Guangdong Academy of Medical Sciences, Guangzhou; Jie Wang, Peking University School of Oncology, Beijing Cancer Hospital and Institute, Beijing; You Lu, Sichuan University, Sichuan; Xiaojin Shi, AstraZeneca, Shanghai, People's Republic of China; James Chih-Hsin Yang, The National Taiwan University Hospital and College of Medicine, Taipei, Taiwan, Republic of China; Sang-We Kim, University of Ulsan College of Medicine; Myung-Ju Ahn, Sungkyunkwan University School of Medicine, Seoul, South Korea; Kazuhiko Nakagawa, Kindai University; Shinji Atagi, Kinkichuo Chest Medical Center, Osaka, Japan; Santiago Ponce, Hospital Universitario 12 de Octubre, Madrid, Spain; Yuri Rukazenkov, AstraZeneca, Cambridge; Vincent Haddad, AstraZeneca, Royston, United Kingdom; Kenneth S. Thress, AstraZeneca, Waltham, MA; and Jean-Charles Soria, Gustave Roussy Cancer Campus and University Paris-Sud, Villejuif, France.

Abstract

Purpose The Iressa Mutation-Positive Multicentre Treatment Beyond ProgRESsion Study (IMPRESS) compared the continuation of gefitinib plus chemotherapy with placebo plus chemotherapy in patients with epidermal growth factor receptor ( EGFR) mutation-positive advanced non-small-cell lung cancer with progression (Response Evaluation Criteria in Solid Tumors 1.1) after first-line gefitinib. Primary results indicated no difference between treatments in terms of progression-free survival (PFS). The current analysis presents final, mature, overall survival (OS) data, together with exploratory analyses that examined whether specific biomarkers, including T790M mutation status, were able to differentiate a relative treatment effect. Patients and Methods Patients were randomly assigned to gefitinib 250 mg or placebo, in addition to cisplatin 75 mg/m2 plus pemetrexed 500 mg/m2 (maximum of six cycles of chemotherapy). EGFR mutation status was determined from plasma-derived circulating free tumor-derived DNA samples (beads, emulsification, amplification, and magnetics digital polymerase chain reaction assay, allelic fraction analysis). Results A total of 265 patients with non-small-cell lung cancer were randomly assigned, and overall data maturity was 66%. Continuation of gefitinib plus cisplatin and pemetrexed was detrimental to OS when compared with placebo plus cisplatin and pemetrexed (hazard ratio [HR], 1.44; 95% CI, 1.07 to 1.94; P = .016; median OS, 13.4 v 19.5 months). The detriment was statistically significant in patients with T790M mutation-positive plasma samples (HR, 1.49; 95% CI, 1.02 to 2.21), whereas statistical significance was not reached in T790M mutation-negative patients (HR, 1.15; 95% CI, 0.68 to 1.94). PFS in T790M mutation-positive patients was similar between treatments, and the difference observed in T790M mutation-negative patients did not reach statistical significance (HR, 0.67; 95% CI, 0.43 to 1.03; P = .0745). Conclusion Final OS data from IMPRESS are supportive of earlier PFS results and are sufficient to warn physicians against the continuation of treatment with first-generation EGFR tyrosine kinase inhibitors beyond radiologic disease progression when chemotherapy is initiated. Plasma biomarker analyses suggest that this effect may be driven by T790M-positive status.

PMID:
28968167
DOI:
10.1200/JCO.2017.73.9250
[Indexed for MEDLINE]

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