Characterization and Clinical Utility of Mutation Detection Using Cell-Free DNA in Patients with Advanced Melanoma.

Tissue-based tests for mutation-positive melanoma involve invasive biopsy procedures, and can lead to an erroneous diagnosis when the tumor samples degrade. Herein, we explored a minimally invasive, cell-free deoxyribonucleic acid (cfDNA)-based platform, to retest patients for mutations. This phase 2 study enrolled adult patients with unresectable/metastatic melanoma. A prescreening testing phase evaluated the concordance between a prior tissue-based mutation test result and a subsequent plasma cfDNA-based test result. A treatment phase evaluated the patients who were confirmed as mutation-positive, and were treated with cobimetinib plus vemurafenib. It was found that 35/54 patients (64.8%) with a mutant status by prior tissue test had a positive  mutation with the cfDNA test. Further, 7/118 patients (5.9%) with a wild-type status had a positive  mutation cfDNA test; tissue retests on archival samples confirmed  mutation positivity in 5/7 patients (71.4%). One of these patients received BRAF pathway-targeted therapy (cobimetinib plus vemurafenib), and had progression-free survival commensurate with previous experience. In the overall cobimetinib plus vemurafenib-treated population, 29/36 patients (80.6%) had an objective response. The median progression-free survival was 13.6 months (95% confidence interval, 9.5-16.5). Cell-free DNA-based tests may be a fast and convenient option to identify mutation status in melanoma patients, and help inform treatment decisions.