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 |
| PMCID: | PMC6341982 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 October 2018 -- Source: Scopus |
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