Brigatinib (BRG) vs crizotinib (CRZ) in anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitor-naive ALK plus non-small cell lung cancer (NSCLC): ALTA-1L final results

Abstract

Background In ALTA-1L planned interim analyses, BRG progression-free survival (PFS) by blinded independent review committee (BIRC) was superior to CRZ. We report final ALTA-1L (NCT02737501) results. Methods Patients (pts) were randomized 1:1 to BRG 180 mg qd (7-day lead-in at 90 mg) or CRZ 250 mg bid. Primary endpoint: PFS by BIRC. Secondary endpoints included intracranial PFS (iPFS; BIRC), overall survival (OS), safety, quality of life (QoL). Results 275 pts randomized (BRG/CRZ, n=137/138); median age 58/60 y; prior chemotherapy (CT) 26%/27%; median CT duration, 71/73 days; baseline brain metastases (BL BM) 29%/30%. As of 29 Jan 2021 (last patient contact), median follow-up was 40.4/15.2 mo, with 166 (73/93) PFS events. BIRC PFS hazard ratio (HR) was 0.48 (95% CI: 0.35–0.66, log-rank P<0.0001); median PFS was 24.0 (95% CI: 18.4–43.2)/11.1 (9.1–13.0) mo; 3-yr PFS rate, 43%/19%. PFS HR by investigator was 0.43 (0.31–0.58; median PFS 30.8 vs 9.2 mo). Median duration of response (DoR) was 33/14 mo by BIRC and 37/11 mo by investigator. Median OS was not reached in either group (events: 41/51; HR 0.81 [0.53–1.22]; 3-yr OS 71%/68%. In pts with BL BM, PFS HR 0.25 (0.14–0.46); OS HR 0.43 (0.21–0.89; Table). Most common grade ≥3 treatment-emergent adverse events (AE): BRG: increased creatine phosphokinase (26%) and lipase (15%), hypertension (14%); CRZ: increased alanine aminotransferase (10%), lipase, (8%), aspartate aminotransferase (7%). Any-grade interstitial lung disease/pneumonitis: 5.9%/2.2%; discontinuation due to AE: 13.2%/8.8%. Median time to worsening in pt-reported global health status/QoL was 26.7/8.3 mo; HR 0.69 (0.49–0.98). Table: 29P Efficacya BRG CRZ P BL brain metastases Measurable, n 18 23 Confirmed iORR, % 78 (52–94b) 26 (10–48b) 0.0014c Median iDoRd, mo 28 (6–NEb) 9 (4–NEb) Any, n 40e 41e PFS events, n (%) 24 (60) 31 (76) HR 0.25 (0.14–0.46b) <0.0001f OS events, n (%) 11 (28) 22 (54) 3-yr OS, % 74 (57–85b) 55 (38–69b) HR 0.43 (0.21–0.89b) 0.0199f 47a 49a iPFS events, n (%) 27 (57) 35 (71) HR 0.29 (0.17–0.51b) <0.0001f , n 97e 97e PFS events, n (%) 49 (51) 62 (64) HR 0.62 (0.43–0.91b) 0.0131f OS events, n (%) 30 (31) 29 (30) 3-yr OS, % 70 (59–78b) 73 (62–81b) HR 1.16 (0.69–1.93b) 0.6027f 90a 89a iPFS events, n (%) 25 (28) 23 (26) HR 0.70 (0.39–1.26b) 0.2410f a BIRC; b 95% CI; c CMH test; d Confirmed responders; e Investigator; f Log-rank Conclusions BRG demonstrated durable overall and intracranial efficacy with manageable tolerability with extended treatment, confirming BRG as a standard of care in treatment-naive ALK+ NSCLC.