Brigatinib in Patients With Alectinib-Refractory ALK-Positive NSCLC. J Thorac Oncol 2018 Oct;13(10):1530-1538
Date
06/24/2018Pubmed ID
29935304Pubmed Central ID
PMC6341982DOI
10.1016/j.jtho.2018.06.005Scopus ID
2-s2.0-85051033461 (requires institutional sign-in at Scopus site) 68 CitationsAbstract
INTRODUCTION: The second-generation anaplastic lymphoma kinase (ALK) inhibitor alectinib recently showed superior efficacy compared to the first-generation ALK inhibitor crizotinib in advanced ALK-rearranged NSCLC, establishing alectinib as the new standard first-line therapy. Brigatinib, another second-generation ALK inhibitor, has shown substantial activity in patients with crizotinib-refractory ALK-positive NSCLC; however, its activity in the alectinib-refractory setting is unknown.
METHODS: A multicenter, retrospective study was performed at three institutions. Patients were eligible if they had advanced, alectinib-refractory ALK-positive NSCLC and were treated with brigatinib. Medical records were reviewed to determine clinical outcomes.
RESULTS: Twenty-two patients were eligible for this study. Confirmed objective responses to brigatinib were observed in 3 of 18 patients (17%) with measurable disease. Nine patients (50%) had stable disease on brigatinib. The median progression-free survival was 4.4 months (95% confidence interval [CI]: 1.8-5.6 months) with a median duration of treatment of 5.7 months (95% CI: 1.8-6.2 months). Among 9 patients in this study who underwent post-alectinib/pre-brigatinib biopsies, 5 had an ALK I1171X or V1180L resistance mutation; of these, 1 had a confirmed partial response and 3 had stable disease on brigatinib. One patient had an ALK G1202R mutation in a post-alectinib/pre-brigatinib biopsy, and had progressive disease as the best overall response to brigatinib.
CONCLUSIONS: Brigatinib has limited clinical activity in alectinib-refractory ALK-positive NSCLC. Additional studies are needed to establish biomarkers of response to brigatinib and to identify effective therapeutic options for alectinib-resistant ALK-positive NSCLC patients.
Author List
Lin JJ, Zhu VW, Schoenfeld AJ, Yeap BY, Saxena A, Ferris LA, Dagogo-Jack I, Farago AF, Taber A, Traynor A, Menon S, Gainor JF, Lennerz JK, Plodkowski AJ, Digumarthy SR, Ou SI, Shaw AT, Riely GJMESH terms used to index this publication - Major topics in bold
AdultAged
Carbazoles
Carcinoma, Non-Small-Cell Lung
Female
Humans
Lung Neoplasms
Male
Middle Aged
Organophosphorus Compounds
Piperidines
Pyrimidines
Retrospective Studies
Young Adult
