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
AuthorsCamidge, D. R.
Kim, H. R.
Ahn, M. J.
Yang, J. C. H.
Han, J. Y.
Hochmair, M. J.
Lee, K. H.
Garcia, Campelo, MR
Kim, D. W.
Gettinger, S. N.
Lin, H. M.
Hanley, M. J.
AffiliationUniversity of Colorado Cancer Center, Aurora, CO.
MetadataShow full item record
AbstractPurpose: 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.
CitationCamidge 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.
JournalJournal of Clinical Oncology
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- Issue date: 2018 Nov 22
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