ctDNA detection at baseline was associated with worse recurrence-free, overall survival in BRAFV600-mutant stage III melanoma
By Elana Gotkine HealthDay Reporter
WEDNESDAY, April 16, 2025 (HealthDay News) — Droplet digital polymerase chain reaction (PCR) measurements of cell-free, circulating tumor DNA (ctDNA) can identify patients with melanoma and a high risk for recurrence before adjuvant targeted therapy, according to a study published online April 15 in The Lancet Oncology.
Mahrukh M. Syeda, from NYU Langone Health in New York City, and colleagues examined whether ctDNA measurements could predict survival outcomes during adjuvant therapy or placebo treatment in stage III melanoma. BRAFV600E or BRAFV600K ctDNA was measured using mutation-specific droplet digital PCR assays in patients aged 18 years or older who were enrolled in the COMBI-AD trial, a double-blind study of oral dabrafenib plus oral trametinib combination therapy versus two matched placebos in resected BRAFV600-mutant stage III melanoma.
The researchers found that ctDNA was detectable in 79 of 597 baseline samples (13 percent). Patients with higher disease substages had a significantly higher ctDNA positivity rate and mutant copies per mL plasma. ctDNA detection as a binary variable was associated with worse recurrence-free survival (hazard ratios, 2.91 and 2.98 in the placebo and combination groups, respectively) and overall survival (hazard ratios, 3.35 and 4.27, respectively). Compared with interferon gamma gene expression or tumor mutational burden, baseline ctDNA was more strongly associated with survival outcomes. Compared with patients with favorable kinetics, those with adverse longitudinal ctDNA kinetics had markedly shorter median recurrence-free survival.
“These findings provide a strong rationale for additional research to improve the clinical sensitivity of these assays and advance clinical trials that investigate the clinical use of incorporating ctDNA measurements into treatment decisions,” the authors write.
Several authors disclosed ties to biopharmaceutical companies, including Novartis, which funded the study.
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