O1-4-2 [Encore]Brigatinib (BRG) vs Crizotinib (CRZ) in Patients (Pts) With ALK Inhibitor-Naive Advanced ALK+ NSCLC from ALTA-1L

• Published in: Annals of oncology Vol. 30; no. Supplement_6
• Main Authors: Yang, James C H, Kim, Hye R, Ahn, Myung-Ju, Han, Ji-Youn, Hochmair, Maximilian J, Lee, Ki H, Delmonte, Angelo, Campelo, Maria R Garcia, Kim, Dong-Wan, Felip, Enriqueta, Califano, Raffaele, Spira, Alexander, Gettinger, Scott, Tiseo, Marcello, Haney, Jeff, Kerstein, David, Popat, Sanjay, Camidge, D R
• Format: Journal Article
• Language: English
• Published: Oxford University Press 01.10.2019
• ISSN: 0923-7534; 1569-8041
• DOI: 10.1093/annonc/mdz339.006

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 6 mo (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.