Dr. Polsky on the Association Between ctDNA and Survival in Melanoma

David Polsky, MD, PhD, the Alfred W. Kopf, MD, Professor of Dermatologic Oncology, Ronald O. Perelman Department of Dermatology Professor in the Department of Pathology, and director of the Pigmented Lesion Service at NYU Langone Health’s Perlmutter Cancer Center, on the association between circulating tumor (ct)DNA and survival in melanoma.

ctDNA is the fraction of DNA in the plasma that comes from the tumor and it is identified by identifying mutations that stem from the tumor, explains Polsky. For example, in BRAF-mutated melanoma, BRAF-mutated DNA can be found in the plasma and measured.

Some studies have shown that the level of circulating BRAF-mutated DNA prior to treatment with BRAF/MEK therapies, such as dabrafenib (Tafinlar) and trametinib (Mekinist), was shown to be associated with survival. If patients had low ctDNA, they had a better survival compared with if they had high ctDNA.

Investigators also examined what would happen at 4 weeks on treatment and found that patients whose ctDNA became undetectable had a doubling in progression-free survival and overall survival. Those findings were observed in patients with a high tumor burden as assessed by lactate dehydrogenase, which is a standard surrogate blood marker for tumor burden, concludes Polsky.