Phase 3 Study of Alectinib vs Crizotinib in ALK-Positive NSCLC (J-ALEX)
In the J-ALEX study, patients in Japan with ALK-positive non–small-cell lung cancer (NSCLC) were randomized to receive either alectinib (300 mg BID) or crizotinib (250 mg BID). They were stratified by ECOG PS (0/1 vs 2), treatment line (first vs second line), and clinical stage (IIIB/IV vs recurrence). The primary end point of this study was progression-free survival (PFS) according to the blinded independent review board. Secondary end points included overall survival, objective response rate (ORR), and safety.
A total of 207 patients were enrolled at 41 centers in Japan between November 2013 and August 2015. Superiority of PFS was demonstrated for alectinib at the second of 3 planned interim analyses. Median PFS was not reached in the alectinib arm (95% confidence interval [CI], 20.3 months to not reached) compared with 10.2 months in the crizotinib arm (95% CI, 8.2-12.0 months). The hazard ratio (HR) was 0.34 (99+% CI, 0.17-0.70; P <0.0001).
These favorable results for PFS were maintained in each relevant subgroup, including line of treatment (first line: HR, 0.30; second line: HR, 0.39), brain metastases at baseline (yes: HR, 0.08; no: HR, 0.39), and clinical stage (stage IIIb/IV: HR, 0.31; postoperative recurrence: HR, 0.49).
Grade 3/4 adverse events (AEs) were observed in 26% of alectinib recipients and 52% of crizotinib recipients. Discontinuation due to AEs was required in 9% and 20% of patients, respectively. Dose interruptions due to AEs occurred in 29% and 74%, respectively. No treatment-related deaths occurred in this study.
Researchers concluded that alectinib demonstrated a clinically significant prolongation of PFS compared with crizotinib in all subgroups with a favorable AE profile. Alectinib was also significantly more effective at suppressing central nervous system (CNS) disease than crizotinib. Alectinib also was more likely to prevent development of new CNS disease. Based on these findings, alectinib represents a potential new standard for first-line ALK-positive NSCLC patients.
Kim YH, et al. WCLC 2016. Abstract MA 07 03. ID 5597.