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Brigatinib Versus Alectinib in ALK-Positive NSCLC After Disease Progression on Crizotinib: Results of Phase 3 ALTA-3 Trial.
- Source :
-
Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer [J Thorac Oncol] 2023 Dec; Vol. 18 (12), pp. 1743-1755. Date of Electronic Publication: 2023 Aug 12. - Publication Year :
- 2023
-
Abstract
- Introduction: This open-label, phase 3 trial (ALTA-3; NCT03596866) compared efficacy and safety of brigatinib versus alectinib for ALK+ NSCLC after disease progression on crizotinib.<br />Methods: Patients with advanced ALK+ NSCLC that progressed on crizotinib were randomized 1:1 to brigatinib 180 mg once daily (7-d lead-in, 90 mg) or alectinib 600 mg twice daily, aiming to test superiority. The primary end point was blinded independent review committee-assessed progression-free survival (PFS). Interim analysis for efficacy and futility was planned at approximately 70% of 164 expected PFS events.<br />Results: The population (N = 248; brigatinib, n = 125; alectinib, n = 123) was notable for long median duration of prior crizotinib (16.0-16.8 mo) and low rate of ALK fusion in baseline circulating tumor DNA (ctDNA; 78 of 232 [34%]). Median blinded independent review committee-assessed PFS was 19.3 months with brigatinib and 19.2 months with alectinib (hazard ratio = 0.97 [95% confidence interval: 0.66-1.42], p = 0.8672]). The study met futility criterion. Overall survival was immature (41 events [17%]). Exploratory analyses pooled across the treatment groups revealed median PFS of 11.1 versus 22.5 months in patients with versus without ctDNA-detectable ALK fusion at baseline (hazard ratio: 0.48 [95% confidence interval: 0.32-0.71]). Treatment-related adverse events in more than 30% of patients (brigatinib, alectinib) were elevated levels of blood creatine phosphokinase (70%, 29%), aspartate aminotransferase (53%, 38%), and alanine aminotransferase (40%, 36%).<br />Conclusions: Brigatinib was not superior to alectinib for PFS in crizotinib-pretreated ALK+ NSCLC. Safety was consistent with the well-established and unique profiles of each drug. The low proportion of patients with ctDNA-detectable ALK fusion may account for prolonged PFS with both drugs in ALTA-3.<br /> (Copyright © 2023 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)
- Subjects :
- Humans
Anaplastic Lymphoma Kinase genetics
Carbazoles pharmacology
Carbazoles therapeutic use
Crizotinib pharmacology
Crizotinib therapeutic use
Disease Progression
Protein Kinase Inhibitors therapeutic use
Carcinoma, Non-Small-Cell Lung pathology
Lung Neoplasms drug therapy
Lung Neoplasms genetics
Lung Neoplasms pathology
Subjects
Details
- Language :
- English
- ISSN :
- 1556-1380
- Volume :
- 18
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer
- Publication Type :
- Academic Journal
- Accession number :
- 37574132
- Full Text :
- https://doi.org/10.1016/j.jtho.2023.08.010