Updated efficacy and safety of the j-alex study comparing alectinib (ALC) with crizotinib (CRZ) in ALK-inhibitor naïve <i>ALK</i> fusion positive non-small cell lung cancer (<i>ALK+</i> NSCLC).

<jats:p> 9064 </jats:p><jats:p> Background: ALC is a highly selective, CNS-active ALK tyrosine kinase inhibitor. In the J-ALEX study, ALC proved superior efficacy and tolerability compared to CRZ at the pre-planned interim analysis at 83 progression free survival (PFS) events (51% of target events) . Here we report the updated data with a further 10 months of follow up. Methods: Patients with advanced ALK+ NSCLC were randomized 1:1 to receive ALC 300 mg b.i.d or CRZ 250 mg b.i.d and stratified by ECOG PS, treatment line, and clinical stage. Study Treatment was continued until disease progression or unacceptable toxicity. The primary endpoint was PFS according to the blinded independent review. Secondary endpoints included investigator-assessed PFS, overall survival, objective response rate and safety. Results: From Nov 2013 to Aug 2015, 207 patients were enrolled. Data cut off for the present analysis was Sep 2016. Median durations of PFS follow up were 20.5 months in the ALC arm and 20.4 months in the CRZ arm with 116 events by independent review observed. The updated PFS HR was 0.38 (95% CI: 0.26-0.55, p< 0.0001). Median PFS was 25.9 months (95% CI: 20.3-not estimated) with ALC and 10.2 months (95% CI: 8.3-12.0) with CRZ. For patients without brain metastasis at baseline (n = 164), ALC prevented CNS metastasis onset compared to CRZ (HR = 0.19, 95% CI: 0.07-0.53). For patients with brain metastasis at baseline (n = 43), ALC also prevented CNS progression compared to CRZ (HR = 0.51, 95% CI: 0.16-1.64). Adverse events (AEs) with frequency of more than 30% were constipation (37.9%) and nasopharyngitis (32.0%) in the ALC arm, while in the CRZ arm nausea (76.0%), diarrhea (74.0%), vomiting (57.7%), visual disturbance (54.8%), dysgeusia (51.9%), constipation (46.2%), increased ALT (32.7%), and increased AST (31.7%) were observed. Grade 3-4 AEs occurred with greater frequency in the CRZ arm (ALC: 32.0% vs CRZ: 56.7%). There were no Grade 5 AEs in either arm. Conclusions: In the updated analysis, ALC consistently showed superior efficacy compared to CRZ in systemic disease and prevention of CNS progression. ALC was also associated with a more favorable tolerability profile than CRZ. Clinical trial information: JapicCTI-132316. </jats:p>