INTRODUCTION: We report updated data from a phase 2 randomized study evaluating brigatinib in crizotinib-refractory anaplastic lymphoma kinase-positive NSCLC. METHODS: Patients were randomized 1:1 to take either oral brigatinib 90 mg once daily (arm A) or 180 mg once daily with a 7-day lead-in at 90 mg (arm B), stratified by central nervous system (CNS) metastases and best response to crizotinib. The primary end point was investigator-assessed confirmed objective response rate per Response Evaluation Criteria in Solid Tumors version 1.1. Secondary end points included independent review committee (IRC)-assessed progression-free survival (PFS), intracranial PFS (iPFS), and overall survival (OS). Exploratory analyses included CNS versus ex-CNS target lesion response and correlation of depth of response with PFS and OS. RESULTS: Among 222 randomized patients (112 and 110 in arms A and B, respectively), 59 (27%) remained on brigatinib at analysis (median follow-up: 19.6 versus 24.3 months). At baseline, 71% and 67% had brain lesions among A and B arms, respectively. Investigator-assessed confirmed objective response rate was 46% versus 56%. Median IRC-assessed PFS was 9.2 months (95% confidence interval: 7.4-12.8) versus 16.7 months (11.6-21.4). Median OS was 29.5 months (18.2-not reached) versus 34.1 months (27.7-not reached). IRC-confirmed intracranial objective response rate in patients with measurable baseline brain lesions was 50% (13 of 26) versus 67% (12 of 18); median duration of intracranial response was 9.4 versus 16.6 months. IRC-assessed iPFS was 12.8 versus 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 once daily with lead-in) continues to demonstrate robust PFS, long iPFS and duration of intracranial response, and high intracranial objective response rate in crizotinib-refractory patients. Depth of response may be an important end point to capture in future targeted therapy trials.
- Huber, R. M.
- Hansen, K. H.
- Paz-Ares Rodriguez, L.
- West, H. L.
- Reckamp, K. L.
- Leighl, N. B.
- Tiseo, M.
- Smit, E. F.
- Kim, D. W.
- Gettinger, S. N.
- Hochmair, M. J.
- Kim, S. W.
- Langer, C. J.
- Ahn, M. J.
- Kim, E. S.
- Kerstein, D.
- Groen, H. J. M.
- Camidge, D. R.
Keywords
- ALK tyrosine kinase receptor
- Anaplastic lymphoma kinase
- Brigatinib
- Non-small cell lung cancer