Brigatinib versus crizotinib in anaplastic lymphoma kinase (ALK) inhibitor-naive advanced alk-positive non-small cell lung cancer: final results of the Phase 3 ALTA-1L trial
AuthorsCamidge, D. R.
Kim, H. R.
Ahn, M. J.
Yang, J. C.
Han, J. Y.
Hochmair, M. J.
Lee, K. H.
Garcia Campelo, M. R.
Kim, D. W.
Spira, A. I.
Gettinger, S. N.
Lin, H. M.
AffiliationUniversity of Colorado Cancer Center, 1665 Aurora Ct, Aurora, CO, USA 80045.
MetadataShow full item record
AbstractIntroduction: In the phase 3 ALTA-1L study of brigatinib in anaplastic lymphoma kinase (ALK) inhibitor-naive advanced ALK+ NSCLC, brigatinib demonstrated superior progression-free survival (PFS) versus crizotinib in 2 planned interim analyses. We report final efficacy, safety, and exploratory results. Methods: Patients were randomized to brigatinib 180 mg once daily (7-day lead-in at 90 mg once daily) or crizotinib 250 mg twice daily. Primary endpoint was blinded independent review committee (BIRC)-assessed PFS. Genetic alterations in plasma cell-free DNA were assessed in relation to clinical efficacy. Results: 275 patients were enrolled (brigatinib, n = 137; crizotinib, n = 138). At study end, (brigatinib median follow-up: 40.4 months), 3-year PFS by BIRC was 43% (brigatinib) versus 19% (crizotinib; median, 24.0 vs 11.1 months; HR: 0.48; 95% CI: 0.35-0.66). Median overall survival (OS) was not reached in either group (HR: 0.81; 95% CI: 0.53-1.22). Post hoc analyses suggested an OS benefit for brigatinib in patients with baseline brain metastases (HR: 0.43; 95% CI: 0.21-0.89). Detectable baseline EML4-ALK fusion variant 3 and TP53 mutation in plasma were associated with poor PFS. Brigatinib demonstrated efficacy superior to crizotinib regardless of EML4-ALK variant and TP53 mutation. Emerging secondary ALK mutations were rare in patients progressing on brigatinib. No new safety signals were observed. Conclusions: At ALTA-1L final analysis, with longer follow-up brigatinib continued to demonstrate superior efficacy and tolerability versus crizotinib in patients with or without poor prognostic biomarkers. The suggested survival benefit with brigatinib in patients with brain metastases warrants future study.
CitationCamidge DR, Kim HR, Ahn M-J, Yang JCH, Han J-Y, Hochmair MJ, et al. Brigatinib versus Crizotinib in Anaplastic Lymphoma Kinase (ALK) Inhibitor–Naive Advanced ALK-Positive Non–Small Cell Lung Cancer: Final Results of the Phase 3 ALTA-1L Trial. Journal of Thoracic Oncology. 2021 Sep.
JournalJournal of Thoracic Oncology
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- Authors: Camidge DR, Kim HR, Ahn MJ, Yang JCH, Han JY, Hochmair MJ, Lee KH, Delmonte A, García Campelo MR, Kim DW, Griesinger F, Felip E, Califano R, Spira A, Gettinger SN, Tiseo M, Lin HM, Gupta N, Hanley MJ, Ni Q, Zhang P, Popat S
- Issue date: 2020 Nov 1
- Brigatinib versus Crizotinib in ALK-Positive Non-Small-Cell Lung Cancer.
- Authors: Camidge DR, Kim HR, Ahn MJ, Yang JC, Han JY, Lee JS, Hochmair MJ, Li JY, Chang GC, Lee KH, Gridelli C, Delmonte A, Garcia Campelo R, Kim DW, Bearz A, Griesinger F, Morabito A, Felip E, Califano R, Ghosh S, Spira A, Gettinger SN, Tiseo M, Gupta N, Haney J, Kerstein D, Popat S
- Issue date: 2018 Nov 22
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- Issue date: 2022 Dec
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- Authors: Garcia Campelo MR, Lin HM, Zhu Y, Pérol M, Jahanzeb M, Popat S, Zhang P, Camidge DR
- Issue date: 2021 May
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- Authors: Huber RM, Hansen KH, Paz-Ares Rodríguez L, West HL, Reckamp KL, Leighl NB, Tiseo M, Smit EF, Kim DW, Gettinger SN, Hochmair MJ, Kim SW, Langer CJ, Ahn MJ, Kim ES, Kerstein D, Groen HJM, Camidge DR
- Issue date: 2020 Mar