Enrollment Trends Among Patients With Melanoma Brain Metastasis in Active Clinical Trials

Abstract

Abstract Purpose The central nervous system is one of the most common first sites of distant metastasis and systemic treatment failure for melanoma patients. These patients have also been traditionally excluded from clinical trials despite check-point inhibitors showing remarkable CNS efficacy. This study aims to determine the current state of prospective melanoma research in regard to inclusion of patients with CNS metastases. Methods Trial data were collected from ClinicalTrials.gov and were excluded if they were specific for other disease types, excluded advanced melanoma, or did not include a systemic anticancer pharmaceutical. Inclusion of active CNS disease and exclusion of CNS disease were the co-primary end points. Results 475 trials were identified and 387 trials met the inclusion criteria. 268 (69.3%) trials excluded patients based on their CNS disease and 12.9% of trials did not specify whether these patients were included. 196 (50.6%) trials excluded patients with any leptomeningeal disease and 41.1% of trials required local treatment for these patients to be included. In univariate analysis, trials not using immunotherapy (IO) therapy and non-pharmaceutical sponsor trials were twice as likely to include patients with active CNS disease. In multivariate analysis IO therapy and inclusion of leptomeningeal disease were associated with CNS disease. Conclusion Although relevant advances in treatment options for metastatic melanoma have greatly improved patient outcomes, many ongoing clinical trials continue to exclude patients with CNS metastasis from participation.