Phase I/II study of alectinib (CH5424802/RO5424802) in patients with alk-rearranged non-small cell lung cancer (NSCLC): Updated results from the AF-001JP trial

Purpose. We investigated the efficacy and safety of the long-term administration of a highly selective anaplastic lymphoma kinase (ALK) inhibitor with a novel scaffold, alectinib, in Japanese patients with ALKrearranged non-small cell lung cancer (NSCLC). Methods. ALK-rearranged NSCLC patients (Pts) naive to ALK inhibitors were treated with alectinib at a dose of 300 mg b.i.d until on the onset of progressive disease. We herein report the efficacy and safety of this treatment according to an independent review at the one-year time point after enrollment of the last patient (as of April 18, 2013). Results. Among the 46 pts in assessed in the phase II portion of this study, the overall response rate was 93.5%(95%CI: 82.1-98.6). The one-year progression free rate was 83% (95%CI: 68-92), although the median progression free survival (PFS) had not been reached at the time of cutoff date. Among the 58 pts treated with alectinib at a dose of 300 mg b.i.d in the phase I and II portions of the AF-001JP study, 42 (72%) remained on the study regimen, with a median treatment duration of 15.8 months. Major treatment-related adverse events included dysgeusia, rashes and increased AST and blood bilirubin levels, mostly of grade 1-2. Conclusions. Alectinib demonstrates long-term efficacy and a favorable benefit-risk profile in ALK inhibitor-naive patients with ALK-rearranged NSCLC.