BRAF-Mutated Metastatic Melanoma: Predicting Therapeutic Response With ctDNA

By: Jenna Carter, PhD
Posted: Wednesday, August 28, 2024

Standard treatment of unresectable metastatic melanoma harboring a BRAF V600 mutation typically includes a combination of BRAF and MEK kinase inhibitors; however, almost half the patients develop resistance within the first year of treatment. A study presented at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting (Abstract 9541) highlighted the relevance of circulating tumor DNA (ctDNA) in predicting outcomes in patients with metastatic melanoma undergoing BRAF and MEK inhibitor treatment. Alexandre Harle, PharmD, PhD, of the Institut de Cancérologie de Lorraine, Université de Lorraine, Nancy, France, and colleagues found that the presence of BRAF mutation at baseline was associated with a significantly lower progression-free survival.

A total of 31 patients with histologically proven advanced melanoma harboring BRAF mutations were included in the OPTIMEL trial. Patients had either metastatic disease or were deemed ineligible for surgery. All participants underwent treatment with BRAF and MEK inhibitors, and blood samples were systematically obtained. Collection days included days 0, 15, 30, 90, 180, 270, and 365 or at the occurrence of disease progression.

Baseline analyses revealed a BRAF mutation in 18 patients (58%); this mutation was associated with a significantly lower progression-free survival (hazard ratio [HR] = 3.42; confidence interval [CI] = 95%, 1.19–9.82; P = .22). Follow-up analyses revealed that BRAF mutation was detected in 19 patients (61%). Additionally, a BRAF variant allele frequency of 2.3% was strongly linked to an objective response to treatment (P < .010), according to the study authors. The absence of BRAF variant detection during follow-up was significantly associated with better outcomes (progression-free survival, 4.01 vs 12.0 months; HR = 28.5; CI = 95%, 7.75–105.0; P < .001). NRAS mutation was linked to treatment resistance and a worse progression-free survival (4.84 vs 10.9 months; HR = 11.6; CI = 95%, 2.76–48.5; P < .001).

Disclosure: For full disclosures of the study authors, visit coi.asco.org.

2024 ASCO Annual Meeting