Dr. Polsky on the Predictive Value of ctDNA 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 predictive value of circulating tumor DNA (ctDNA) in BRAF-mutant melanoma.

In an analysis led by Polsky, ctDNA monitoring was found to be clinically valid in predicting whether patients with unresectable, metastatic BRAF-mutant melanoma would benefit from either dabrafenib (Tafinlar) alone or in combination with trametinib (Mekinist). At baseline, the amount of ctDNA was predictive of survival.

This is the first study to show the predictive value of ctDNA, as prior studies have only been able to detect its presence or lack thereof, explains Polsky. Moreover, there was a high sensitivity rate of 93% of patients who had a BRAF V600E mutation in their plasma. With this platform, investigators were able to quantify these levels with outcomes.

For example, the samples that were collected at week 4 were predictive of survival benefit. If patients had no detectable ctDNA at week 4, they had a progression-free survival and overall survival that was approximately double that of those who had persistent ctDNA detected at week 4.

Further follow-up may indicate that ctDNA could become a monitoring tool that could direct treatment. For example, if patients have positive ctDNA for a prolonged period of time after starting treatment, adding an additional treatment might be considered, explains Polsky. On the other hand, if patients have no evidence of ctDNA during treatment, they might not require additional therapy. However, this hypothesis will have be validated in future studies before it can be applied to practice.