Brigatinib versus crizotinib in ALK-positive non-small-cell lung cancer
File(s)
Published version
Author(s)
Type
Journal Article
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 .).
Date Issued
2018-11-22
Date Acceptance
2018-09-01
Citation
New England Journal of Medicine, 2018, 379, pp.2027-2039
ISSN
0028-4793
Publisher
Massachusetts Medical Society
Start Page
2027
End Page
2039
Journal / Book Title
New England Journal of Medicine
Volume
379
Copyright Statement
© 2018 Massachusetts Medical Society.
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/30280657
Subjects
Science & Technology
Life Sciences & Biomedicine
Medicine, General & Internal
General & Internal Medicine
ANAPLASTIC LYMPHOMA KINASE
EML4-ALK FUSION GENE
OPEN-LABEL
BRAIN METASTASES
SINGLE-ARM
INHIBITOR
EGFR
CHEMOTHERAPY
RESISTANCE
CERITINIB
11 Medical And Health Sciences
Publication Status
Published
Coverage Spatial
United States
Date Publish Online
2018-09-25