Medline ® Abstract for Reference 32
of 'Systemic therapy for advanced non-small cell lung cancer with an activating mutation in the epidermal growth factor receptor'
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.
Mok TSK, Kim SW, Wu YL, Nakagawa K, Yang JJ, Ahn MJ, Wang J, Yang JC, Lu Y, Atagi S, Ponce S, Shi X, Rukazenkov Y, Haddad V, Thress KS, Soria JC
J Clin Oncol. 2017;
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/m(2) plus pemetrexed 500 mg/m(2) (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.
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, As