Brigatinib (BRG) vs Crizotinib (CRZ) in Patients (Pts) With ALK Inhibitor-Naive Advanced ALK+ NSCLC from ALTA-1L

Abstract

Abstract Background We report results of the first interim analysis (IA) of BRG vs CRZ in ALK TKI-naive, ALK+ NSCLC from ALTA-1L (NCT02737501). Methods This open-label, multicenter study enrolled pts with advanced ALK+ NSCLC who had ≤1 prior systemic therapy; asymptomatic CNS metastases were allowed. Pts were randomized 1:1 to BRG 180 mg QD with 7-day lead-in at 90 mg or CRZ 250 mg BID. Primary endpoint: blinded independent review committee (BIRC)-assessed PFS (RECIST v1.1). Secondary efficacy endpoints included BIRC-assessed ORR, intracranial (i) ORR (iORR), and PFS (iPFS). IAs were planned at 50% and 75% of 198 expected PFS events. Results 275 pts were randomized (BRG/CRZ, n = 137/138); median age: 58/60 y. 26%/27% received prior chemotherapy for advanced disease; 29%/30% had baseline brain metastases. At data cutoff (19Feb2018), median follow-up of BRG/CRZ was 11.0/9.25 mo. With 99 PFS events, BRG met the prespecified threshold for statistical superiority vs CRZ in the primary endpoint, BIRC-assessed PFS (HR 0.49, 95% CI 0.33-0.74, log-rank P=0.0007); BRG median PFS (95% CI) was not reached (NR; NR) vs CRZ 9.8 months (9.0-12.9). Investigator-assessed PFS HR 0.45 (95% CI 0.30-0.68), log-rank P=0.0001. Confirmed ORR for BRG was 71% (62-78) vs CRZ 60% (51-68). In pts with any iCNS disease (BRG/CRZ, n = 43/47), confirmed iORR was 67% (51-81) vs 17% (8-31), P Conclusions BRG showed a statistically and clinically significant improvement in PFS vs CRZ in ALK inhibitor-naive ALK+ NSCLC.