Dr. Polsky on Validating ctDNA as a Biomarker in BRAF-Mutant Melanoma

David Polsky, MD, PhD, Alfred W. Kopf, MD Professor of Dermatologic Oncology, Ronald O. Perelman Department of Dermatology, professor, Department of Pathology, and director, Pigmented Lesion Service, NYU Langone’s Perlmutter Cancer Center, discusses the next steps that have to be taken to validate the clinical utility of circulating tumor DNA (ctDNA) as a biomarker in BRAF-mutant melanoma.

A study led by Polsky demonstrated the clinical validity of ctDNA monitoring in predicting whether patients with advanced BRAF-mutant melanoma would benefit from either dabrafenib (Tafinlar) alone or in combination with trametinib (Mekinist). Investigators need to evaluate additional timepoints as they only had week 4 samples for the first analysis. Further analysis could show better predictive value on which to base a survival model, says Polsky.

If additional follow-up reveals consistent findings, investigators would like to launch a clinical trial randomizing patients to a prespecified second-line therapy. At the time of progression, patients would switch to another agent and then could be randomized to receive therapy based on a rise in their ctDNA versus radiographic progression, which is the standard of care. That type of a design would demonstrate whether the marker has clinical utility, not just clinical validity, concludes Polsky.