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/NEJMoa1704795 出版商提供的全文 http://www.nejm.org/doi/full/10.1056/NEJMoa1704795 |
其它资讯
摘要Background
Alectinib, a highly selective inhibitor of anaplastic lymphoma kinase (ALK), has shown systemic and central nervous system (CNS) efficacy in the treatment of ALK-positive non-small-cell lung cancer (NSCLC). We investigated alectinib as compared with crizotinib in patients with previously untreated, advanced ALK-positive NSCLC, including those with asymptomatic CNS disease.
Methods
In a randomized, open-label, phase 3 trial, we randomly assigned 303 patients with previously untreated, advanced ALK-positive NSCLC to receive either alectinib (600 mg twice daily) or crizotinib (250 mg twice daily). The primary end point was investigator-assessed progression-free survival. Secondary end points were independent review committee-assessed progression-free survival, time to CNS progression, objective response rate, and overall survival.
Results
During a median follow-up of 17.6 months (crizotinib) and 18.6 months (alectinib), an event of disease progression or death occurred in 62 of 152 patients (41%) in the alectinib group and 102 of 151 patients (68%) in the crizotinib group. The rate of investigator-assessed progression-free survival was significantly higher with alectinib than with crizotinib (12-month event-free survival rate, 68.4% [95% confidence interval (CI), 61.0 to 75.9] with alectinib vs. 48.7% [95% CI, 40.4 to 56.9] with crizotinib; hazard ratio for disease progression or death, 0.47 [95% CI, 0.34 to 0.65]; P<0.001); the median progression-free survival with alectinib was not reached. The results for independent review committee-assessed progression-free survival were consistent with those for the primary end point. A total of 18 patients (12%) in the alectinib group had an event of CNS progression, as compared with 68 patients (45%) in the crizotinib group (cause-specific hazard ratio, 0.16; 95% CI, 0.10 to 0.28; P<0.001). A response occurred in 126 patients in the alectinib group (response rate, 82.9%; 95% CI, 76.0 to 88.5) and in 114 patients in the crizotinib group (response rate, 75.5%; 95% CI, 67.8 to 82.1) (P=0.09). Grade 3 to 5 adverse events were less frequent with alectinib (41% vs. 50% with crizotinib).
Conclusions
As compared with crizotinib, alectinib showed superior efficacy and lower toxicity in primary treatment of ALK-positive NSCLC.
着者Peters S1, Camidge DR1, Shaw AT1, Gadgeel S1, Ahn JS1, Kim DW1, Ou SI1, Pérol M1, Dziadziuszko R1, Rosell R1, Zeaiter A1, Mitry E1, Golding S1, Balas B1, Noe J1, Morcos PN1, Mok T1; ALEX Trial Investigators
期刊名称New England Journal of Medicine
出版年份2017
月份6
日期6
出版社Boston, Massachusetts Medical Society
出版地United States
国际标準期刊号0028-4793
电子国际标準期刊号1533-4406
语言英式英语
关键词NSCLC
