Alectinib versus Crizotinib in Untreated ALK -Positive Non–Small-Cell Lung Cancer

作者：Solange Peters, D. Ross Camidge, Alice Tsang Shaw, Shirish M. Gadgeel, Jin Seok Ahn, Dong‐Wan Kim, Sai‐Hong Ignatius Ou, Maurice Pérol, Rafał Dziadziuszko, Rafael Rosell, Ali Hassan Zeaiter, Emmanuel Mitry, Sophie Golding, Bogdana I Balas, Johannes Noé, Peter N. Morcos, Tony S.K. Mok · 发表于：New England Journal of Medicine · 年份：2017 · DOI：10.1056/nejmoa1704795 · 被引用次数：2520 · 研究领域：Lung Cancer Treatments and Mutations、Lung Cancer Research Studies、Lung Cancer Diagnosis and Treatment

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 wit...