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 5 137; crizotinib, n 5 138). 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 5 .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 5 .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.
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 / 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, M. R.; Kim, D. -W.; Griesinger, F.; Felip, E.; Califano, R.; Spira, A.; Gettinger, S. N.; Tiseo, M.; Lin, H. M.; Gupta, N.; Hanley, M. J.; Ni, Q.; Zhang, P.; Popat, S.. - In: JOURNAL OF CLINICAL ONCOLOGY. - ISSN 0732-183X. - 38:31(2020), pp. 3592-3603. [10.1200/JCO.20.00505]
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
Tiseo M.;
2020-01-01
Abstract
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 5 137; crizotinib, n 5 138). 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 5 .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 5 .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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
