Brigatinib versus crizotinib in ALK-positive non-small-cell lung cancer
Journal
New England Journal of Medicine
Journal Volume
379
Journal Issue
21
Pages
2027-2039
Date Issued
2018
Author(s)
Camidge D.R
Kim H.R
Ahn M.-J
Han J.-Y
Lee J.-S
Hochmair M.J
Li J.Y.-C
Chang G.-C
Lee K.H
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 S.N
Tiseo M
Gupta N
Haney J
Kerstein D
Popat S.
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 followup 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.). Copyright ? 2018 Massachusetts Medical Society.
SDGs
Other Subjects
anaplastic lymphoma kinase; brigatinib; crizotinib; ALK protein, human; anaplastic lymphoma kinase; antineoplastic agent; brigatinib; crizotinib; organophosphorus compound; pyrimidine derivative; adult; advanced cancer; aged; Article; cancer growth; cancer mortality; controlled study; female; follow up; human; long term survival; major clinical study; male; multicenter study; non small cell lung cancer; phase 3 clinical trial; priority journal; progression free survival; randomized controlled trial; treatment response; antagonists and inhibitors; brain tumor; chemistry; clinical trial; comparative study; Kaplan Meier method; lung tumor; middle aged; non small cell lung cancer; pathology; secondary; very elderly; Adult; Aged; Aged, 80 and over; Anaplastic Lymphoma Kinase; Antineoplastic Agents; Brain Neoplasms; Carcinoma, Non-Small-Cell Lung; Crizotinib; Female; Humans; Kaplan-Meier Estimate; Lung Neoplasms; Male; Middle Aged; Organophosphorus Compounds; Progression-Free Survival; Pyrimidines
Publisher
Massachussetts Medical Society
Type
journal article