Brigatinib in Patients With Crizotinib-Refractory Anaplastic Lymphoma Kinase–Positive Non–Small-Cell Lung Cancer: A Randomized, Multicenter Phase II Trial

作者：Dong‐Wan Kim, Marcello Tiseo, Myung‐Ju Ahn, Karen L. Reckamp, Karin Holmskov Hansen, Sang‐We Kim, Rudolf Maria Huber, Howard West, Harry J.M. Groen, Maximilian Johannes Hochmair, Natasha B. Leighl, Scott N. Gettinger, Corey Jay Langer, Luis G. Paz-Ares Rodríguez, Egbert Frederik Smit, Edward S. Kim, William M. Reichmann, Frank G. Haluska, David Kerstein, D. Ross Camidge · 发表于：Journal of Clinical Oncology · 年份：2017 · DOI：10.1200/jco.2016.71.5904 · 被引用次数：585 · 研究领域：Lung Cancer Treatments and Mutations、Chronic Lymphocytic Leukemia Research、Chronic Myeloid Leukemia Treatments

Purpose Most crizotinib-treated patients with anaplastic lymphoma kinase gene ( ALK)-rearranged non-small-cell lung cancer (ALK-positive NSCLC) eventually experience disease progression. We evaluated two regimens of brigatinib, an investigational next-generation ALK inhibitor, in crizotinib-refractory ALK-positive NSCLC. Patients and Methods Patients were stratified by brain metastases and best response to crizotinib. They were randomly assigned (1:1) to oral brigatinib 90 mg once daily (arm A) or 180 mg once daily with a 7-day lead-in at 90 mg (180 mg once daily [with lead-in]; arm B). Investigator-assessed confirmed objective response rate (ORR) was the primary end point. Results Of 222 patients enrolled (arm A: n = 112, 109 treated; arm B: n = 110, 110 treated), 154 (69%) had baseline brain metastases and 164 of 222 (74%) had received prior chemotherapy. With 8.0-month median follow-up, investigator-assessed confirmed ORR was 45% (97.5% CI, 34% to 56%) in arm A and 54% (97.5% CI, 43% to 65%) in arm B. Investigator-assessed median progression-free survival was 9.2 months (95% CI, 7.4 to 15.6) and 12.9 months (95% CI, 11.1 to not reached) in arms A and B, respectively. Independent review committee-assessed intracranial ORR in patients with measurable brain metastases at baseline was 42% (11 of 26 patients) in arm A and 67% (12 of 18 patients) in arm B. Common treatment-emergent adverse events were nausea (arm A/B, 33%/40%), diarrhea (arm A/B, 19%/38%), headache (arm A/B, 28%...