Dr. Polsky on the Clinical Validity of ctDNA in BRAF-Mutant Melanoma

David Polsky, MD, PhD, the Alfred W. Kopf, MD, Professor of Dermatologic Oncology, Ronald O. Perelman Department of Dermatology Professor, Department of Pathology, and director of the Pigmented Lesion Service, NYU Langone Health’s Perlmutter Cancer Center, discusses the use of circulating tumor DNA (ctDNA) in the COMBI-d trial on melanoma.

NYU Langone Health’s Perlmutter Cancer Center uses droplet digital polymerase chain reaction in their laboratories, which is known to be a highly sensitive and specific method to detect ctDNA, says Polsky. Data from the COMBI-d trial presented at the 2019 ASCO Annual Meeting showed that ctDNA monitoring is clinically valid in predicting whether patients with unresectable, metastatic BRAF-mutant melanoma will benefit from dabrafenib (Tafinlar) alone or in combination with trametinib (Mekinist).

Investigators saw a very high detection rate of 93% in these patients, says Polsky; this means that investigators were able to detect the BRAF mutation in the patient’s tumor prior to treatment in 93% of patients, which is the highest percentage reported to date, according to Polsky.

Although other sequencing-based assays have advantages over ctDNA and are able to detect multiple mutations at the same time, the sensitivity of ctDNA is thought to be the highest when looking at a single molecule target at a time, concludes Polsky.