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Analysis Demonstrates Correlation Between Presence of ctDNA and Survival in Melanoma

David Polsky, MD, PhD
Published Online:6:14 PM, Fri July 26, 2019


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.

Polsky says this can become a monitoring tool, should additional studies and time points be investigated further. For example, patients with persistently positive ctDNA after beginning treatment may seek additional treatment, while patients that come back negative for ctDNA on treatment can wait to see if their disease progresses further and add additional treatment if necessary. However, further investigation is necessary.
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