Final PFS analysis and safety data from the phase III J-ALEX study of alectinib (ALC) vs. crizotinib (CRZ) in ALK-inhibitor naïve ALK-positive non-small cell lung cancer (ALK+ NSCLC).

Abstract

9092 Background: The primary analysis of the J-ALEX (JapicCTI-132316) study for the ALK-inhibitor naïve ALK+ NSCLC demonstrated superior progression-free survival (PFS) of ALC compared with CRZ (HR 0.34, 99.7% CI 0.17–0.71, stratified log-rank p < 0·0001) by the Independent Review Facility (IRF) (data cutoff, December 3 2015, Hida et al., Lancet 2017) . Here, we report the final PFS and OS 2nd interim data (data cutoff, June 30 2018). Methods: ALK+ NSCLC (by IHC and FISH or RT-PCR) patients were randomized 1:1 either to receive ALC (300 mg BID, n = 103) or CRZ (250 mg BID, n = 104). Stratification factors included ECOG PS, treatment line, and clinical stage. Primary endpoint was PFS according to the blinded IRF. Secondary endpoints included OS, objective response rate, and safety. Results: After a median follow-up of 42.2 months in the ALC arm and 42.4 months in the CRZ arm, an event of disease progression or death occurred in 54% and 86% in the ALC arm and the CRZ arm, respectively. The final PFS HR was 0.37 (95%CI 0.26-0.52): median IRF-PFS was 34.1 months (95%CI 22.1– not estimated) in the ALC arm and 10.2 months (95%CI 8.3–12.0) in the CRZ arm. HRs for the time to CNS progression or death was 0.33 (95%CI 0.11–0.93) and 0.20 (95%CI 0.08–0.49) with or without CNS metastases at baseline, respectively. The 2nd interim analysis of OS was still immature (events 30.1% in the ALC arm, 31.7% in the CRZ arm; stratified HR 0.80, 95%CI 0.35–1.82). Most of patients (77.9%) in the CRZ arm received ALC as a subsequent therapy whereas only 10.7% of patients in the ALC arm received CRZ. Proportion of patients with grade 3–4 AEs (37% vs 61%), AEs leading to interruption (40% vs 82%) or discontinuation (12% vs 23%) were lower in the ALC arm than the CRZ arm. There were no treatment-related deaths in either arm. Conclusions: In the final PFS analysis, ALC continued to demonstrate the superiority in IRF-PFS in ALK-inhibitor naïve ALK+ NSCLC regardless of baseline CNS metastases with a favorable safety profile. The updated result of OS will be presented in the future congress. Clinical trial information: JapicCTI-132316.