Brigatinib versus Crizotinib in ALK-Positive Non-Small-Cell Lung Cancer
Authors
Camidge, DRKim, HR
Ahn, MJ
Yang, JC
Han, JY
Lee, JS
Hochmair, MJ
Li, JY
Chang, GC
Lee, KH
Gridelli, C
Delmonte, A
Garcia, CR
Kim, DW
Bearz, A
Griesinger, F
Morabito, A
Felip, E
Califano, Raffaele
Ghosh, S
Spira, A
Gettinger, SN
Tiseo, M
Gupta, N
Haney, J
Kerstein, D
Popat, S
Affiliation
University of Colorado Cancer Center, Aurora; Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of MedicineIssue Date
2018
Metadata
Show full item recordAbstract
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
Camidge DR, Kim HR, Ahn M-J, Yang JC-H, Han J-Y, Lee J-S, et al. Brigatinib versus Crizotinib in ALK-Positive Non�Small-Cell Lung Cancer. New England Journal of Medicine. 2018 Nov 22;379(21):2027�39.Journal
N Engl J MedDOI
10.1056/NEJMoa1810171PubMed ID
30280657Additional Links
https://dx.doi.org/10.1056/NEJMoa1810171Type
ArticleLanguage
enae974a485f413a2113503eed53cd6c53
10.1056/NEJMoa1810171
Scopus Count
Collections
Related articles
- 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.
- Authors: Camidge DR, Kim HR, Ahn MJ, Yang JCH, Han JY, Hochmair MJ, Lee KH, Delmonte A, García Campelo MR, Kim DW, Griesinger F, Felip E, Califano R, Spira A, Gettinger SN, Tiseo M, Lin HM, Gupta N, Hanley MJ, Ni Q, Zhang P, Popat S
- Issue date: 2020 Nov 1
- Brigatinib in Patients With Crizotinib-Refractory Anaplastic Lymphoma Kinase-Positive Non-Small-Cell Lung Cancer: A Randomized, Multicenter Phase II Trial.
- Authors: Kim DW, Tiseo M, Ahn MJ, Reckamp KL, Hansen KH, Kim SW, Huber RM, West HL, Groen HJM, Hochmair MJ, Leighl NB, Gettinger SN, Langer CJ, Paz-Ares Rodríguez LG, Smit EF, Kim ES, Reichmann W, Haluska FG, Kerstein D, Camidge DR
- Issue date: 2017 Aug 1
- Activity and safety of brigatinib in ALK-rearranged non-small-cell lung cancer and other malignancies: a single-arm, open-label, phase 1/2 trial.
- Authors: Gettinger SN, Bazhenova LA, Langer CJ, Salgia R, Gold KA, Rosell R, Shaw AT, Weiss GJ, Tugnait M, Narasimhan NI, Dorer DJ, Kerstein D, Rivera VM, Clackson T, Haluska FG, Camidge DR
- Issue date: 2016 Dec
- Exploratory Analysis of Brigatinib Activity in Patients With Anaplastic Lymphoma Kinase-Positive Non-Small-Cell Lung Cancer and Brain Metastases in Two Clinical Trials.
- Authors: Camidge DR, Kim DW, Tiseo M, Langer CJ, Ahn MJ, Shaw AT, Huber RM, Hochmair MJ, Lee DH, Bazhenova LA, Gold KA, Ou SI, West HL, Reichmann W, Haney J, Clackson T, Kerstein D, Gettinger SN
- Issue date: 2018 Sep 10
- Brigatinib vs alectinib in crizotinib-resistant advanced anaplastic lymphoma kinase-positive non-small-cell lung cancer (ALTA-3).
- Authors: Popat S, Liu G, Lu S, Song G, Ma X, Yang JC
- Issue date: 2021 Nov