Brigatinib versus crizotinib in advanced alk inhibitor-naive alk-positive non-small cell lung cancer: second interim analysis of the phase III ALTA-1L Trial
Authors
Camidge, D. R.Kim, H. R.
Ahn, M. J.
Yang, J. C. H.
Han, J. Y.
Hochmair, M. J.
Lee, K. H.
Delmonte, A.
Garcia, Campelo, MR
Kim, D. W.
Griesinger, F.
Felip, E.
Califano, Raffaele
Spira, A.
Gettinger, S. N.
Tiseo, M.
Lin, H. M.
Gupta, N.
Hanley, M. J.
Ni, Q.
Zhang, P.
Popat, S.
Affiliation
University of Colorado Cancer Center, Aurora, CO.Issue Date
2020
Metadata
Show full item recordAbstract
Purpose: Brigatinib, a next-generation anaplastic lymphoma kinase (ALK) inhibitor, demonstrated superior progression-free survival (PFS) and improved health-related quality of life (QoL) versus crizotinib in advanced ALK inhibitor-naive ALK-positive non-small cell lung cancer (NSCLC) at first interim analysis (99 events; median brigatinib follow-up, 11.0 months) in the open-label, phase III ALTA-1L trial (ClinicalTrials.gov identifier: NCT02737501). We report results of the second prespecified interim analysis (150 events). Methods: Patients with ALK inhibitor-naive advanced ALK-positive NSCLC were randomly assigned 1:1 to brigatinib 180 mg once daily (7-day lead-in at 90 mg once daily) or crizotinib 250 mg twice daily. The primary end point was PFS as assessed by blinded independent review committee (BIRC). Investigator-assessed efficacy, blood samples for pharmacokinetic assessments, and patient-reported outcomes were also collected. Results: Two hundred seventy-five patients were randomly assigned (brigatinib, n = 137; crizotinib, n = 138). With median follow-up of 24.9 months for brigatinib (150 PFS events), brigatinib showed consistent superiority in BIRC-assessed PFS versus crizotinib (hazard ratio [HR], 0.49 [95% CI, 0.35 to 0.68]; log-rank P < .0001; median, 24.0 v 11.0 months). Investigator-assessed PFS HR was 0.43 (95% CI, 0.31 to 0.61; median, 29.4 v 9.2 months). No new safety concerns emerged. Brigatinib delayed median time to worsening of global health status/QoL scores compared with crizotinib (HR, 0.70 [95% CI, 0.49 to 1.00]; log-rank P = .049). Brigatinib daily area under the plasma concentration-time curve was not a predictor of PFS (HR, 1.005 [95% CI, 0.98 to 1.031]; P = .69). Conclusion: Brigatinib represents a once-daily ALK inhibitor with superior efficacy, tolerability, and QoL over crizotinib, making it a promising first-line treatment of ALK-positive NSCLC.Citation
Camidge DR, Kim HR, Ahn M-J, Yang JCH, Han J-Y, Hochmair MJ, et al. Brigatinib Versus Crizotinib in Advanced ALK Inhibitor�Naive ALK-Positive Non�Small Cell Lung Cancer: Second Interim Analysis of the Phase III ALTA-1L Trial. Journal of Clinical Oncology. 2020:JCO.20.00505.Journal
Journal of Clinical OncologyDOI
10.1200/jco.20.00505PubMed ID
32780660Additional Links
https://dx.doi.org/10.1200/jco.20.00505Type
ArticleLanguage
enae974a485f413a2113503eed53cd6c53
10.1200/jco.20.00505
Scopus Count
Collections
Related articles
- 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
- Health-related quality of life in the randomized phase III trial of brigatinib vs crizotinib in advanced ALK inhibitor-naive ALK + non-small cell lung cancer (ALTA-1L).
- Authors: Garcia Campelo MR, Lin HM, Zhu Y, Pérol M, Jahanzeb M, Popat S, Zhang P, Camidge DR
- Issue date: 2021 May
- Brigatinib Versus Crizotinib in ALK Inhibitor-Naive Advanced ALK-Positive NSCLC: Final Results of Phase 3 ALTA-1L Trial.
- Authors: Camidge DR, Kim HR, Ahn MJ, Yang JCH, Han JY, Hochmair MJ, Lee KH, Delmonte A, Garcia Campelo MR, Kim DW, Griesinger F, Felip E, Califano R, Spira AI, Gettinger SN, Tiseo M, Lin HM, Liu Y, Vranceanu F, Niu H, Zhang P, Popat S
- Issue date: 2021 Dec
- Efficacy and Safety of Brigatinib Compared With Crizotinib in Asian vs. Non-Asian Patients With Locally Advanced or Metastatic ALK-Inhibitor-Naive ALK+ Non-Small Cell Lung Cancer: Final Results From the Phase III ALTA-1L Study.
- Authors: Ahn MJ, Kim HR, Yang JCH, Han JY, Li JY, Hochmair MJ, Chang GC, Delmonte A, Lee KH, Campelo RG, Gridelli C, Spira AI, Califano R, Griesinger F, Ghosh S, Felip E, Kim DW, Liu Y, Zhang P, Popat S, Camidge DR
- Issue date: 2022 Dec
- Activity and safety of brigatinib in ALK-rearranged non-small-cell lung cancer and other malignancies: a single-arm, open-label, phase 1/2 trial.
- Authors: Gettinger SN, Bazhenova LA, Langer CJ, Salgia R, Gold KA, Rosell R, Shaw AT, Weiss GJ, Tugnait M, Narasimhan NI, Dorer DJ, Kerstein D, Rivera VM, Clackson T, Haluska FG, Camidge DR
- Issue date: 2016 Dec