TY - JOUR
T1 - Brigatinib Versus Crizotinib in Advanced ALK Inhibitor–Naive ALK-Positive Non–Small Cell Lung Cancer
T2 - Second Interim Analysis of the Phase III ALTA-1L Trial
AU - Camidge, D. Ross
AU - Kim, Hye Ryun
AU - Ahn, Myung Ju
AU - Yang, James C.H.
AU - Han, Ji Youn
AU - Hochmair, Maximilian J.
AU - Lee, Ki Hyeong
AU - Delmonte, Angelo
AU - García Campelo, Maria Rosario
AU - Kim, Dong Wan
AU - Griesinger, Frank
AU - Felip, Enriqueta
AU - Califano, Raffaele
AU - Spira, Alexander
AU - Gettinger, Scott N.
AU - Tiseo, Marcello
AU - Lin, Huamao M.
AU - Gupta, Neeraj
AU - Hanley, Michael J.
AU - Ni, Quanhong
AU - Zhang, Pingkuan
AU - Popat, Sanjay
N1 - Funding Information:
and Lela Creutz, PhD, of Peloton Advantage, Parsippany, NJ, an OPEN Health company, and funded by Millennium Pharmaceuticals. Supported by National Health Service funding to the Royal Marsden Hospital/ Institute of Cancer Research NIHR Biomedical Research Centre (S.P.).
Publisher Copyright:
© 2020 by American Society of Clinical Oncology
PY - 2020/11/1
Y1 - 2020/11/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85094933151&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85094933151&partnerID=8YFLogxK
U2 - 10.1200/JCO.20.00505
DO - 10.1200/JCO.20.00505
M3 - Article
C2 - 32780660
AN - SCOPUS:85094933151
SN - 0732-183X
VL - 38
SP - 3592
EP - 3603
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 31
ER -