吉非替尼
培美曲塞
医学
肺癌
肿瘤科
内科学
化疗
T790米
表皮生长因子受体
危险系数
吉西他滨
顺铂
癌症
置信区间
作者
Tony Mok,Sang‐We Kim,Yi‐Long Wu,Kazuhiko Nakagawa,Jin-Ji Yang,Myung‐Ju Ahn,Jie Wang,James Chih‐Hsin Yang,You Lü,Shinji Atagi,Santiago Ponce,Xiaojin Shi,Yuri Rukazenkov,Vincent Haddad,Kenneth S. Thress,Jean‐Charles Soria
标识
DOI:10.1200/jco.2017.73.9250
摘要
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.
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