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

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<0.0001. BRG median iPFS was NR (11 mo‐NR) vs CRZ 6mo (4‐9); HR 0.27 (95% CI 0.13‐0.54); log‐rank P<0.0001. In pts with measurable iCNS disease (BRG/ CRZ, n=18/21), confirmed iORR was BRG 78% (52‐94) vs CRZ 29% (11‐52); P=0.0028. Most common grade ≥3 TEAEs for BRG were increased CPK (16.2%) and lipase (13.2%), hypertension (9.6%), and for CRZ were increased ALT (9.5%), AST (5.8%), and lipase (5.1%). Any grade ILD/pneumonitis (BRG/CRZ): 3.7%/2.2%; discontinuations due to AE: 11.8%/8.8%. Conclusions: BRG showed a statistically and clinically significant improvement in PFS vs CRZ in ALK inhibitor‐naive ALK+ NSCLC.