Brigatinib in patients With alectinib-refractory ALK-positive NSCLC Journal Article


Authors: Lin, J. J.; Zhu, V. W.; Schoenfeld, A. J.; Yeap, B. Y.; Saxena, A.; Ferris, L. A.; Dagogo-Jack, I.; Farago, A. F.; Taber, A.; Traynor, A.; Menon, S.; Gainor, J. F.; Lennerz, J. K.; Plodkowski, A. J.; Digumarthy, S. R.; Ou, S. H. I.; Shaw, A. T.; Riely, G. J.
Article Title: Brigatinib in patients With alectinib-refractory ALK-positive NSCLC
Abstract: 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. © 2018 International Association for the Study of Lung Cancer
Keywords: adult; cancer chemotherapy; clinical article; controlled study; human tissue; treatment response; aged; gene mutation; constipation; fatigue; advanced cancer; diarrhea; drug dose reduction; drug efficacy; drug safety; drug withdrawal; treatment duration; liver dysfunction; cancer patient; progression free survival; drug eruption; mucosa inflammation; nausea; myalgia; cohort analysis; medical record review; retrospective study; cancer resistance; alanine aminotransferase blood level; aspartate aminotransferase blood level; coughing; drug dose escalation; dyspnea; fever; pneumonia; confidence interval; alanine aminotransferase; aspartate aminotransferase; multicenter study; creatine kinase; drug substitution; abnormally high substrate concentration in blood; leucine; lung biopsy; glycine; amylase; arginine; resistance; valine; triacylglycerol lipase; creatine kinase blood level; alk; non small cell lung cancer; anaplastic lymphoma kinase; nsclc; clinical outcome; crizotinib; human; male; female; priority journal; article; alectinib; brigatinib
Journal Title: Journal of Thoracic Oncology
Volume: 13
Issue: 10
ISSN: 1556-0864
Publisher: Elsevier Inc.  
Date Published: 2018-10-01
Start Page: 1530
End Page: 1538
Language: English
DOI: 10.1016/j.jtho.2018.06.005
PROVIDER: scopus
PUBMED: 29935304
DOI/URL:
Notes: Article -- Export Date: 1 October 2018 -- Source: Scopus
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  1. Gregory J Riely
    378 Riely