Among patients receiving targeted therapy for advanced melanoma, BRAF V600-mutant cell-free circulating tumor DNA (ctDNA) measurements potentially could predict clinical outcome, according to a study published online Feb. 12 in The Lancet Oncology.
Mahrukh M. Syeda, from NYU Langone Health in New York City, and colleagues examined whether baseline ctDNA levels and kinetics could predict survival outcomes among patients aged 18 years and older with melanoma enrolled in two clinical trials: COMBI-d, involving previously untreated patients with BRAF V600 mutation-positive unresectable or metastatic melanoma, and COMBI-MB, enrolling patients with BRAF V600 mutation-positive metastatic melanoma and brain metastases. The relationship between mutant copy number and efficacy end points was examined.
ctDNA was detected in pretreatment samples from 320 of 345 patients in COMBI-d and in 34 of 38 patients in COMBI-MB. The researchers found that independent of baseline lactate dehydrogenase levels, elevated baseline BRAF V600 mutation-positive ctDNA levels predicted worse overall survival outcomes in COMBI-d. Patients enrolled in COMBI-d were stratified by a ctDNA cut point of 64 copies/mL of plasma for survival outcomes; this was validated in the COMBI-MB cohort. There was a significant association for undetectable ctDNA at week 4 with extended progression-free and overall survival in COMBI-d, especially in patients with elevated lactate dehydrogenase levels.
“Although this gene-based test focuses on tumors with BRAF V600 mutations, we believe it will be similarly useful for melanomas that have other mutations, such as defects in the NRAS and TERT genes, which are also commonly mutated in this disease,” Syeda said in a statement.
Several authors disclosed financial ties to biopharmaceutical companies, including Novartis Pharmaceuticals, which funded the study.