Brigatinib (BRG) vs crizotinib (CRZ) in the phase III ALTA-1L trial

Abstract

Background: We report results of the first interim analysis (IA) from the ALTA-1L study of BRG vs CRZ in anaplastic lymphoma kinase (ALK) inhibitor-naive, ALKpositive non-small cell lung cancer (ALK+ NSCLC; NCT02737501). Methods: This open-label, multicenter study enrolled patients (pts) with advanced ALK+ NSCLC. Eligible pts had ≥1 prior systemic therapy for advanced NSCLC. Asymptomatic central nervous system (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 was blinded independent review committee (BIRC)-assessed progression-free survival (PFS; RECIST v1.1); secondary efficacy endpoints included BIRC-assessed objective response rate (ORR), intracranial ORR (iORR), and intracranial 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 (years) 58/60. 26%/27% received prior chemotherapy for advanced disease, and 29%/30% had baseline brain metastases. At data cutoff (19 Feb 2018), with a median follow-up of 11.0/9.3 months (BRG/CRZ) and 99 PFS events, BRG met the prespecified threshold for statistical superiority vs CRZ in the primary endpoint of BIRC-assessed PFS (HR 0.49; 95% CI, 0.33-0.74; log-rank P=0.0007); BRG median PFS was not reached (NR; 95% CI, NR) vs CRZ 9.8 months (95% CI, 9.0-12.9). Investigator-assessed PFS HR 0.45 (95% CI, 0.30-0.68); log-rank P=0.0001. Table shows additional efficacy data. Most common grade ≥3 treatment-emergent adverse events (AEs): BRG: increased blood creatine phosphokinase (16.2%) and lipase (13.2%), hypertension (9.6%); CRZ: increased alanine aminotransferase (9.5%), aspartate aminotransferase (5.8%), and lipase (5.1%). Any grade interstitial lung disease/pneumonitis: BRG, 3.7%; CRZ, 2.2%. Discontinuations due to AE (BRG/CRZ): 11.8%/8.8%. Conclusions: BRG showed a statistically and clinically significant improvement in PFS vs CRZ in ALK inhibitor-naive ALK+ NSCLC.