Reference Detail

Ref Type Journal Article
PMID (29935304)
Authors 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, Ignatius Ou SH, Shaw AT, Riely GJ
Title Brigatinib in Patients with Alectinib-Refractory ALK-Positive Non-Small Cell Lung Cancer: A Retrospective Study.
Journal Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer
Vol
Issue
Date 2018 Jun 20
URL
Abstract Text 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.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.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.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.

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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
Drug Name Trade Name Synonyms Drug Classes Drug Description
Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
ALK rearrange ALK D1203N lung non-small cell carcinoma predicted - resistant Brigatinib Case Reports/Case Series Actionable In a clinical case study, ALK D1203N was identified at disease progression while on Alunbrig (brigatinib) treatment in a patient with ALK-positive non-small cell lung cancer (PMID: 29935304). 29935304
ALK rearrange ALK V1180L lung non-small cell carcinoma predicted - sensitive Brigatinib Case Reports/Case Series Actionable In a clinical study, Alunbrig (brigatinib) treatment resulted in 1 partial response and 1 stable disease in a total of 2 patients with Alecensa (alectinib)-refractory, ALK-rearranged non-small cell lung cancer with an acquired ALK V1180L (PMID: 29935304). 29935304
ALK rearrange ALK I1171N lung non-small cell carcinoma predicted - sensitive Brigatinib Case Reports/Case Series Actionable In a clinical study, Alunbrig (brigatinib) treatment resulted in stable disease in 2 patients with Alecensa (alectinib)-refractory, ALK-rearranged non-small cell lung cancer with an acquired ALK I1171N (PMID: 29935304). 29935304
ALK rearrange ALK I1171N MET amp lung non-small cell carcinoma predicted - resistant Brigatinib Case Reports/Case Series Actionable In a clinical case study, MET amplification was identified together with a pre-existing ALK I1171N at disease progression while on Alunbrig (brigatinib) treatment in a patient with ALK-positive non-small cell lung cancer (PMID: 29935304). 29935304
ALK rearrange ALK V1180L lung non-small cell carcinoma predicted - resistant Alectinib Case Reports/Case Series Actionable In a clinical study, ALK V1180L was identified in post-progression biopsies of 2 non-small cell lung cancer patients harboring an ALK rearrangement after Alecensa (alectinib) treatment (PMID: 29935304). 29935304
ALK rearrange ALK G1202R lung non-small cell carcinoma predicted - resistant Brigatinib Case Reports/Case Series Actionable In a clinical case study, Alunbrig (brigatinib) treatment resulted in progressive disease in a patient with ALK-rearranged non-small cell lung cancer refractory to Alecensa (alectinib) treatment, ALK G1202R was identified in post-brigatinib biopsy (PMID: 29935304). 29935304
ALK rearrange lung non-small cell carcinoma sensitive Brigatinib Clinical Study Actionable In a retrospective analysis, Alunbrig (brigatinib) demonstrated limited efficacy, resulting in an objective response rate of 17% (3/18) and stable disease in 50% (9/18) of patients with Alecensa (alectinib) refractory, ALK-positive non-small cell lung cancer, with a median progression-free survival of 4.4 months (PMID: 29935304). 29935304
ALK rearrange ALK I1171T lung non-small cell carcinoma predicted - resistant Alectinib Case Reports/Case Series Actionable In a clinical case study, ALK I1171T was identified in the post-progression biopsy of a non-small cell lung cancer patient harboring an ALK rearrangement after Alecensa (alectinib) treatment (PMID: 29935304). 29935304
ALK rearrange ALK I1171T lung non-small cell carcinoma predicted - resistant Brigatinib Case Reports/Case Series Actionable In a clinical case study, Alunbrig (brigatinib) treatment resulted in progressive disease in a patient with Alecensa (alectinib)-refractory, ALK-rearranged non-small cell lung cancer with an acquired ALK I1171T (PMID: 29935304). 29935304
ALK rearrange ALK V1180L ALK L1196M ALK G1202R lung non-small cell carcinoma predicted - resistant Brigatinib Case Reports/Case Series Actionable In a clinical case study, ALK G1202R and ALK L1196M were identified at disease progression while on Alunbrig (brigatinib) treatment in liquid biopsy of a patient with ALK-positive non-small cell lung cancer also harboring an ALK V1180L (PMID: 29935304). 29935304