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
Journal
Journal of Clinical Oncology
Journal Volume
38
Journal Issue
31
Pages
3592-3603
Date Issued
2020
Author(s)
Camidge D.R.
Kim H.R.
Ahn M.-J.
Han J.-Y.
Hochmair M.J.
Lee K.H.
Delmonte A.
Garc?a Campelo M.R.
Kim D.-W.
Griesinger F.
Felip E.
Califano R.
Spira A.
Gettinger S.N.
Tiseo M.
Lin H.M.
Gupta N.
Hanley M.J.
Ni Q.
Zhang P.
Popat S.
Abstract
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. ? 2020 by American Society of Clinical Oncology
SDGs
Other Subjects
amylase; anaplastic lymphoma kinase; brigatinib; creatine kinase; crizotinib; lipase B; anaplastic lymphoma kinase; antineoplastic agent; brigatinib; crizotinib; organophosphorus compound; pyrimidine derivative; adult; advanced cancer; aged; bradycardia; brain metastasis; Conference Paper; constipation; controlled study; coughing; decreased appetite; dermatitis; diarrhea; drug dose reduction; drug efficacy; drug safety; drug withdrawal; dysgeusia; dyspepsia; dysphagia; dyspnea; epistaxis; erythema; fatigue; female; follow up; gastroesophageal reflux; human; human tissue; hypertension; hypertransaminasemia; hypoalbuminemia; hypocalcemia; hypokalemia; hypotension; interstitial lung disease; major clinical study; male; multiple cycle treatment; myalgia; nausea; non small cell lung cancer; open study; overall survival; patient-reported outcome; peripheral edema; phase 3 clinical trial; plasma concentration-time curve; pleura effusion; pneumonia; priority journal; pruritus; quality of life; randomized controlled trial; rash; treatment duration; upper abdominal pain; visual impairment; vomiting; adolescent; blood; clinical trial; comparative study; lung tumor; metabolism; middle aged; multicenter study; non small cell lung cancer; survival rate; young adult; Adolescent; Adult; Aged; Anaplastic Lymphoma Kinase; Antineoplastic Agents; Carcinoma, Non-Small-Cell Lung; Crizotinib; Female; Humans; Lung Neoplasms; Male; Middle Aged; Organophosphorus Compounds; Progression-Free Survival; Pyrimidines; Quality of Life; Survival Rate; Young Adult
Publisher
American Society of Clinical Oncology
Type
conference paper