David Polsky, MD, PhD

David Polsky, MD, PhD, a professor of dermatology in the Ronald L. Perlman Department of Dermatology at NYU Langone Health&rsquo;s Perlmutter Cancer Center, discusses methods to identify circulating tumor DNA (ctDNA) in patients with melanoma.

In the laboratory at Polsky&rsquo;s institution, they use the Droplet Digital&trade; PCR (polymerase chain reaction), which is a highly sensitive and specific method to detect ctDNA in patients with melanoma. He and his colleagues presented data at the American Society of Clinical Oncology (ASCO) 2019 Annual Meeting showing a 93% detection rate in the COMBI-d trial of patients with unresectable or metastatic melanoma. They were able to detect the

mutation in the tumor prior to treatment in 93% of patients, which has been the highest number reported so far in this setting, according to Polsky.

Sequencing-based assays have advantages over the ctDNA identification method Polsky used and are able to detect multiple mutations at the same time. He says the sensitivity of ctDNA is thought to be the highest when looking at a single molecule target at a time.

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David Polsky, MD, PhD, discusses methods to identify circulating tumor DNA in patients with melanoma.

How Physicians Can Detect ctDNA in Melanoma

David Polsky, MD, PhD, professor of dermatology at NYU Langone Health, discusses the findings from a liquid biopsy analysis of the COMBI-d trial (NCT01584648), which is a phase III trial investigating the combination of dabrafenib (Tafinlar) and trametinib (Mekinist) or dabrafenib alone in patients with BRAF V600E/Kmutant melanoma. Investigators found an association between the presence of baseline circulating tumor DNA (ctDNA) and a poor prognosis with the treatment of BRAF inhibitors.

Baseline ctDNA was predictive of survival, in contrast with findings from other studies. There was a high detection rate of 93% of patients with detectable BRAF V600E mutations using the digital droplet technology. This is the highest rate found across similar studies to date, says Polsky. The platform allowed investigators to quantify the amount of ctDNA very precisely.

In this analysis, investigators also analyzed the levels of ctDNA as opposed to just the presence or absence. The levels did correlate with outcome, Polsky adds. At week 4, the levels also appeared predictive of survival benefit. Overall, 40% of patients with no detectable ctDNA as of week 4 had an extended progression-free survival and overall survival compared to the 60% of patients who were still positive for ctDNA.

David Polsky, MD, PhD, discusses the findings from a liquid biopsy analysis of the COMBI-d trial, which is a phase III trial investigating the combination of dabrafenib and trametinib or dabrafenib alone in patients with BRAF V600E/K&ndash;mutant melanoma. Investigators found an association between the presence of baseline circulating tumor DNA (ctDNA) and a poor prognosis with the treatment of BRAF inhibitors.

David Polsky, MD, PhD | Authors

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How Physicians Can Detect ctDNA in Melanoma

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