Publication in refereed journal
香港中文大学研究人员 ( 现职)
| 莫树锦教授 (肿瘤学系) |
全文
| 数位物件识别号 (DOI) http://dx.doi.org/10.1056/NEJMoa1612674 |
引用次数
Web of Sciencehttp://aims.cuhk.edu.hk/converis/portal/Publication/25WOS source URL
Scopushttp://aims.cuhk.edu.hk/converis/portal/Publication/40Scopus source URL
其它资讯
摘要Background
Osimertinib is an epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) that is selective for both EGFR-TKI sensitizing and T790M resistance mutations in patients with non–small-cell lung cancer. The efficacy of osimertinib as compared with platinum-based therapy plus pemetrexed in such patients is unknown.
Methods
In this randomized, international, open-label, phase 3 trial, we assigned 419 patients with T790M-positive advanced non–small-cell lung cancer, who had disease progression after first-line EGFR-TKI therapy, in a 2:1 ratio to receive either oral osimertinib (at a dose of 80 mg once daily) or intravenous pemetrexed (500 mg per square meter of body-surface area) plus either carboplatin (target area under the curve, 5 [AUC5]) or cisplatin (75 mg per square meter) every 3 weeks for up to six cycles; maintenance pemetrexed was allowed. In all the patients, disease had progressed during receipt of first-line EGFR-TKI therapy. The primary end point was investigator-assessed progression-free survival.
Results
The median duration of progression-free survival was significantly longer with osimertinib than with platinum therapy plus pemetrexed (10.1 months vs. 4.4 months; hazard ratio; 0.30; 95% confidence interval [CI], 0.23 to 0.41; P<0.001). The objective response rate was significantly better with osimertinib (71%; 95% CI, 65 to 76) than with platinum therapy plus pemetrexed (31%; 95% CI, 24 to http://aims.cuhk.edu.hk/converis/portal/Publication/40) (odds ratio for objective response, 5.39; 95% CI, 3.47 to 8.48; P<0.001). Among 144 patients with metastases to the central nervous system (CNS), the median duration of progression-free survival was longer among patients receiving osimertinib than among those receiving platinum therapy plus pemetrexed (8.5 months vs. 4.2 months; hazard ratio, 0.32; 95% CI, 0.21 to 0.49). The proportion of patients with adverse events of grade 3 or higher was lower with osimertinib (23%) than with platinum therapy plus pemetrexed (47%).
Conclusions
Osimertinib had significantly greater efficacy than platinum therapy plus pemetrexed in patients with T790M-positive advanced non–small-cell lung cancer (including those with CNS metastases) in whom disease had progressed during first-line EGFR-TKI therapy.
着者Mok TS, Wu YL, Ahn MJ, Garassino MC, Kim HR, Ramalingam SS, Shepherd FA, He Y, Akamatsu H, Theelen WSME, Lee CK, Sebastian M, Templeton A, Mann H, Marotti M, Ghiorghiu S, Papadimitrakopoulou VA
期刊名称New England Journal of Medicine
出版年份2017
月份2
日期16
卷号376
期次7
出版社Massachusetts Medical Society
出版地United States
页次629 - 6http://aims.cuhk.edu.hk/converis/portal/Publication/40
国际标準期刊号0028-4793
电子国际标準期刊号1533-4http://aims.cuhk.edu.hk/converis/portal/Publication/406
语言英式英语
关键词Positive Lung Cancer, EGFR
