Brigatinib in Patients with Alectinib-Refractory ALK-Positive Non-Small Cell Lung Cancer: A Retrospective Study
| Autor: | Ashish Saxena, Smitha Menon, Alice T. Shaw, Adam J. Schoenfeld, Jochen K. Lennerz, Jessica J. Lin, Anna F. Farago, Angela Taber, Ibiayi Dagogo-Jack, Anne M. Traynor, Gregory J. Riely, Viola W. Zhu, Justin F. Gainor, Sai-Hong Ignatius Ou, Beow Y. Yeap, Lorin A. Ferris, Subba R. Digumarthy, Andrew J. Plodkowski |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Pulmonary and Respiratory Medicine Oncology Alectinib Adult Male medicine.medical_specialty Lung Neoplasms Brigatinib medicine.drug_class Carbazoles Article 03 medical and health sciences Young Adult 0302 clinical medicine Organophosphorus Compounds Piperidines Internal medicine hemic and lymphatic diseases Carcinoma Non-Small-Cell Lung Biopsy medicine Anaplastic lymphoma kinase Humans Aged Retrospective Studies Crizotinib medicine.diagnostic_test business.industry Receptor Protein-Tyrosine Kinases Retrospective cohort study Middle Aged medicine.disease ALK inhibitor 030104 developmental biology Pyrimidines 030220 oncology & carcinogenesis Female business Progressive disease medicine.drug |
| Popis: | BACKGROUND: The second-generation ALK inhibitor alectinib recently demonstrated superior efficacy compared to the first-generation ALK inhibitor crizotinib in advanced anaplastic lymphoma kinase (ALK)-rearranged non-small cell lung cancer (NSCLC), establishing alectinib as the new standard first-line therapy. Brigatinib, another second-generation ALK inhibitor, has demonstrated 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 nine patients in this study who underwent post-alectinib/pre-brigatinib biopsies, five had an ALK I1171X or V1180L resistance mutation; of these, one had a confirmed partial response and three 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. |
| Databáze: | OpenAIRE |
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