Brigatinib versus Crizotinib in ALK-Positive Non-Small-Cell Lung Cancer.
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ICR Authors
Authors
Camidge, DR
Kim, HR
Ahn, M-J
Yang, JC-H
Han, J-Y
Lee, J-S
Hochmair, MJ
Li, JY-C
Chang, G-C
Lee, KH
Gridelli, C
Delmonte, A
Garcia Campelo, R
Kim, D-W
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
Kim, HR
Ahn, M-J
Yang, JC-H
Han, J-Y
Lee, J-S
Hochmair, MJ
Li, JY-C
Chang, G-C
Lee, KH
Gridelli, C
Delmonte, A
Garcia Campelo, R
Kim, D-W
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
Document Type
Journal Article
Date
2018-11
Date Accepted
Date Available
Abstract
Background Brigatinib, a next-generation anaplastic lymphoma kinase (ALK) inhibitor, has robust efficacy in patients with ALK-positive non-small-cell lung cancer (NSCLC) that is refractory to crizotinib. The efficacy of brigatinib, as compared with crizotinib, in patients with advanced ALK-positive NSCLC who have not previously received an ALK inhibitor is unclear.Methods In an open-label, phase 3 trial, we randomly assigned, in a 1:1 ratio, patients with advanced ALK-positive NSCLC who had not previously received ALK inhibitors to receive brigatinib at a dose of 180 mg once daily (with a 7-day lead-in period at 90 mg) or crizotinib at a dose of 250 mg twice daily. The primary end point was progression-free survival as assessed by blinded independent central review. Secondary end points included the objective response rate and intracranial response. The first interim analysis was planned when approximately 50% of 198 expected events of disease progression or death had occurred.Results A total of 275 patients underwent randomization; 137 were assigned to brigatinib and 138 to crizotinib. At the first interim analysis (99 events), the median follow-up was 11.0 months in the brigatinib group and 9.3 months in the crizotinib group. The rate of progression-free survival was higher with brigatinib than with crizotinib (estimated 12-month progression-free survival, 67% [95% confidence interval {CI}, 56 to 75] vs. 43% [95% CI, 32 to 53]; hazard ratio for disease progression or death, 0.49 [95% CI, 0.33 to 0.74]; P<0.001 by the log-rank test). The confirmed objective response rate was 71% (95% CI, 62 to 78) with brigatinib and 60% (95% CI, 51 to 68) with crizotinib; the confirmed rate of intracranial response among patients with measurable lesions was 78% (95% CI, 52 to 94) and 29% (95% CI, 11 to 52), respectively. No new safety concerns were noted.Conclusions Among patients with ALK-positive NSCLC who had not previously received an ALK inhibitor, progression-free survival was significantly longer among patients who received brigatinib than among those who received crizotinib. (Funded by Ariad Pharmaceuticals; ALTA-1L ClinicalTrials.gov number, NCT02737501 .).
Citation
The New England journal of medicine, 2018, 379 (21), pp. 2027 - 2039
Source Title
Publisher
ISSN
0028-4793
eISSN
1533-4406
Collections
Research Team
Thoracic Oncology