Brigatinib in Crizotinib-Refractory ALK+ Non-Small Cell Lung Cancer: 2-Year Follow-up on Systemic and Intracranial Outcomes in the Phase 2 ALTA Trial.

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J Thorac Oncol


INTRODUCTION: We report updated data from a phase 2 randomized study evaluating brigatinib in crizotinib-refractory anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC).

METHODS: Patients were randomized 1:1 to oral brigatinib 90 mg qd (arm A) or 180 mg qd with 7-day lead-in at 90 mg (B), stratified by central nervous system (CNS) metastases and best response to crizotinib. Primary endpoint was investigator-assessed confirmed objective response rate (cORR) per Response Evaluation Criteria In Solid Tumors v1.1. Secondary endpoints included independent review committee (IRC)-assessed progression-free survival (PFS), intracranial PFS (iPFS) and overall survival (OS). Exploratory analyses included CNS vs ex-CNS target lesion response and correlation of depth of response with PFS and OS.

RESULTS: Among 222 randomized patients (A/B: n=112/110), 59 (27%) remained on brigatinib at analysis (median follow-up: 19.6/24.3 months in A/B). At baseline, 71%/67% had brain lesions. Investigator-assessed cORR was 46%/56%. Median IRC-assessed PFS was 9.2 months (95% confidence interval, 7.4-12.8)/16.7 months (11.6-21.4). Median OS was 29.5 months (18.2-not reached [NR])/34.1 months (27.7-NR). IRC-confirmed intracranial ORR (iORR) in patients with measurable baseline brain lesions was 50% (13/26)/67% (12/18); median duration of intracranial response (iDOR) was 9.4/16.6 months. IRC-assessed iPFS was 12.8/18.4 months. Across arms, median IRC-assessed PFS was 1.9, 5.5, 11.1, 16.7, and 15.6 months for patients with no, 1%-25%, 26%-50%, 51%-75%, and 76%-100% target lesion shrinkage, respectively. No new safety findings were observed with longer follow-up.

CONCLUSIONS: Brigatinib (180 mg qd with lead-in) continues to demonstrate robust PFS, long iPFS and iDOR, and high iORR in crizotinib-refractory patients. Depth of response may be an important endpoint to capture in future targeted therapy trials.

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