Systemic and intracranial efficacy of brigatinib vs.crizotinib: updated results from the ALTA-1L Trial

Abstract

Background: At ALTA-1L (NCT02737501) first interim analysis (IA1), brigatinib demonstrated superior BIRC-assessed PFS and iPFS vs crizotinib. We report IA2 results, planned at w75% of 198 expected PFS events. Methods: Patients with TKI-naive advanced ALK+ NSCLC were randomized 1:1 to brigatinib 180 mg qd (7-day lead-in at 90 mg) or crizotinib 250 mg bid. Endpoints: Primary, BIRC-assessed PFS (RECIST v1.1); secondary included confirmed ORR and iORR, and iPFS (BIRC). Results: 275 patients were randomized (brigatinib/crizotinib, n¼137/ 138); median age, 58/60 years; prior chemotherapy, 26%/27%; baseline brain metastases (BIRC), 34%/36%; brain radiotherapy, 13%/ 14% (WBRT/SRS balanced across arms). At data cutoff (28 June 2019, median follow-up [brigatinib/crizotinib], 24.9/15.2 months, 150 PFS events): BIRC-assessed PFS HR, 0.49 (95% CI, 0.35e0.68, log-rank P<0.0001); brigatinib mPFS, 24.0 months (95% CI, 18.5eNE) vs crizotinib 11.0 months (9.2e12.9). Investigator-assessed PFS HR was 0.43 (95% CI, 0.31e0.61, median 29.4 vs 9.2 months). OS was immature (total events: 33/37, brigatinib/crizotinib). In patients with baseline brain metastases, PFS HR was 0.25; data were less mature in brigatinib patients without brain metastases. Additional results in Table. Radiological overall disease progression occurred in (brigatinib vs crizotinib) 54 (39%) vs 74 (54%) patients (BIRC) and 50 (36%) vs 84 (61%) (investigator); of these, brain was first site of progression more frequently with crizotinib vs brigatinib: 31 (42%) vs 17 (31%) patients (BIRC); 22 (26%) vs 7 (14%) (investigator). Most common TEAEs grade 3: brigatinib: increased CPK (24.3%) and lipase (14.0%), hypertension (11.8%); crizotinib: increased ALT (10.2%), AST (6.6%), lipase (6.6%). Brigatinib significantly delayed median time to deterioration vs crizotinib for global health score/QoL (log-rank P¼0.0485), emotional and social functioning, fatigue, nausea and vomiting, appetite loss, constipation. Conclusions: Brigatinib demonstrated superior systemic and intracranial efficacy vs crizotinib in all patients with TKInaive ALK+ NSCLC and in patients with baseline brain metastases.