Efficacy and safety of brigatinib in patients with ALK TKI-naive advanced ALK+ NSCLC: Integrated analysis of the ALTA-1L and J-ALTA trials

Objectives: Brigatinib approval as a first-line anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitor (TKI) for advanced ALK+ non-small cell lung cancer (NSCLC) is supported by results of a non-Japanese global phase 3 trial (ALTA-1L) and a separate phase 2 trial conducted in Japan (J-ALTA). To evaluate outcomes in a larger global patient population, we conducted an integrated analysis of pooled efficacy and safety data from ALTA-1L and J-ALTA. Materials and methods: ALTA-1L (NCT02737501) and J-ALTA (NCT03410108) were open-label, multicenter studies of patients with advanced or metastatic ALK+ NSCLC. ALTA-1L and an expansion cohort of J-ALTA enrolled patients who were ALK TKI naive. Patients with stable or asymptomatic brain metastases were allowed. Brigatinib 180 mg was administered once daily following 7-day lead-in at 90 mg. Primary endpoints were blinded independent review committee (IRC)–assessed progression-free survival (PFS) in ALTA-1L and IRC-assessed 12-month PFS in the J-ALTA ALK TKI-naive cohort. Secondary endpoints included IRC-assessed objective response rate (ORR), duration of response (DOR), intracranial ORR, overall survival (OS), and safety. Results: Overall, 169 patients were allocated to brigatinib in ALTA-1L (n = 137) or J-ALTA (n = 32). In the pooled population (median follow-up: 35.8 months), 34 % of patients were aged ≥65 years, 28 % had baseline brain metastases, and 26 % had received prior chemotherapy. Median PFS by IRC was 29.3 months (95 % CI: 23.9–44.7). Confirmed ORR was 79 % (95 % CI, 72 %–85 %). Median DOR was 38.1 months. Intracranial ORR was 66 % in patients with any brain metastases and 70 % in patients with measurable brain metastases. Three-year OS was 74 %. Grade 3/4 adverse events occurred in 74 % of patients, most commonly increased blood creatine phosphokinase (31 %), hypertension (18 %), and increased lipase (16 %). Conclusion: Brigatinib demonstrated clinically meaningful systemic and intracranial efficacy in patients with ALK TKI-naive ALK+ NSCLC. Safety results were consistent with the known profile for brigatinib.