Sensitivity of plasma BRAFmutant and NRASmutant cell-free DNA assays to detect metastatic melanoma in patients with low RECIST scores and non-RECIST disease progression

摘要: Melanoma lacks a clinically useful blood-based biomarker of disease activity to help guide patient management. To determine whether measurements circulating, cell-free, tumor-associated BRAF(mutant) and NRAS(mutant) DNA (ctDNA) have higher sensitivity than LDH detect metastatic prior treatment initiation upon progression we studied patients with unresectable stage IIIC/IV melanoma receiving BRAF inhibitor therapy or immune checkpoint blockade at least 3 plasma samples obtained during their course. Levels ctDNA were determined using droplet digital PCR (ddPCR) assays. Among available levels elevated in 12/15 (80%) 6/20 (30%) (p = 0.006) respectively. In RECIST scores <5 cm initiation, 5/7 (71%) compared which was 1/13 (8%) 0.007). all events the modified bootstrapped sensitivities for 82% 40% respectively, median difference 42% (95% confidence interval, 27%-58%; P < 0.001). addition, 13/16 (81%) instances non-RECIST progression, including 10/12 (83%) new brain metastases. comparison 8/16 (50%) 6/12 Overall, had events. has potential be monitoring activity.