Updated efficacy and safety data from the global phase III ALEX study of alectinib (ALC) vs crizotinib (CZ) in untreated advanced ALK+ NSCLC.

9043Background: The primary ALEX (NCT02075840) analysis showed superior investigator (INV)-assessed PFS with ALC vs CZ (HR 0.47, 95% CI 0.34–0.65, p<0.001; median 11.1 months [m] CZ, not estimable [NE] ALC) in untreated ALK+ NSCLC. We report updated data (cutoff Dec 1 2017). Methods: ALEX enrolled patients (pts) with stage IIIB/IV ALK+ NSCLC (by central IHC) and no prior systemic therapy for advanced NSCLC; asymptomatic CNS metastases (mets) were allowed. Pts were randomized 1:1 to receive ALC 600mg BID (n = 152) or CZ 250mg BID (n = 151). Primary endpoint: PFS (INV, RECIST v1.1), with q8w CNS imaging in all pts. Secondary endpoints: ORR, time to CNS progression, DOR, OS, and safety. Results: With 10m longer follow-up (median 22.8m CZ vs 27.8m ALC), ALC significantly reduced risk of disease progression/death by 57% vs CZ (ITT; stratified HR 0.43, 95% CI 0.32–0.58): median PFS (INV) was 34.8m ALC vs 10.9m CZ. Median PFS by baseline (BL) CNS mets status was 27.7m ALC vs 7.4m CZ (HR 0.35, 95% CI 0.22–0.56) i...