Molecular Features of Resected Melanoma Brain Metastases, Clinical Outcomes, and Responses to Immunotherapy.
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ABSTRACT:
SUBMITTER: Vasudevan HN
PROVIDER: S-EPMC10436135 | biostudies-literature | 2023 Aug
REPOSITORIES: biostudies-literature
Publications
Molecular Features of Resected Melanoma Brain Metastases, Clinical Outcomes, and Responses to Immunotherapy.
Vasudevan Harish N HN Delley Cyrille C Chen William C WC Mirchia Kanish K Pan Sixuan S Shukla Poojan P Aabedi Alex A AA Nguyen Minh P MP Morshed Ramin A RA Young Jacob S JS Boreta Lauren L Fogh Shannon E SE Nakamura Jean L JL Theodosopoulos Philip V PV Phillips Joanna J Hervey-Jumper Shawn L SL Daras Mariza M Pike Luke L Aghi Manish K MK Tsai Katy K Raleigh David R DR Braunstein Steve E SE Abate Adam R AR
JAMA network open 20230801 8
<h4>Importance</h4>Central nervous system (CNS)-penetrant systemic therapies have significantly advanced care for patients with melanoma brain metastases. However, improved understanding of the molecular landscape and microenvironment of these lesions is needed to both optimize patient selection and advance treatment approaches.<h4>Objective</h4>To evaluate how bulk and single-cell genomic features of melanoma brain metastases are associated with clinical outcome and treatment response.<h4>Desig ...[more]
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Project description:PurposeThis study aimed to identify baseline clinical features associated with the outcomes of patients enrolled in the COMBI-MB phase II study of dabrafenib and trametinib treatment in patients with V600 BRAF-mutant metastatic melanoma with melanoma brain metastases (MBM). Exploratory biomarker analysis was also conducted as part of the synergistic COMBI-BRV trial (BRV116521), to identify molecular and immunologic changes associated with dabrafenib in MBMs and extracranial metastases (ECM).Patients and methodsPost hoc analysis was performed for baseline features of patients (n = 125) enrolled in COMBI-MB. Analyses were performed to identify baseline clinical features associated with intracranial response rate (ICRR), progression-free survival (PFS), and overall survival (OS).Exploratory biomarker analysis was performed on biospecimen collected in the COMBI-BRV trial in which patients with BRAF-mutant, resectable MBM were treated with dabrafenib for 10 to 14 days prior to craniotomy. Accessible ECM were resected or biopsied at the time of craniotomy. Biospecimens underwent molecular and immunologic profiling for comparative analyses.ResultsIn COMBI-MB baseline treatment with corticosteroids was independently associated with lower ICRR [39% vs. 63%; OR, 0.323; 95 % confidence interval (CI), 0.105-0.996; P = 0.049] and shorter PFS (HR, 1.93; 95% CI, 1.06-3.51; P = 0.031). Additional significant associations identified in the multivariate analysis were improved PFS in patients with a BRAFV600E genotype (HR, 0.565; 95% CI, 0.321-0.996; P = 0.048) and improved OS in patients with Eastern Cooperative Oncology Group 0 (HR, 0.44; 95% CI, 0.25-0.78; P = 0.005).ConclusionsCorticosteroid treatment was associated with reduced ICRR and PFS in COMBI-MB, similar to results with immunotherapy for MBMs. Baseline corticosteroid treatment is a key factor to consider in MBM patient management and clinical trial design/interpretation.
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Project description: Not available
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