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Soo Park, MD
Soo Park, MD
Posted: Monday, July 8, 2024
Use of MEK inhibitors in patients with BRAF V600/NRAS Q61 wild-type melanoma whose disease progressed after immune checkpoint inhibitors typically results in skin toxicity. However, combining a BRAF inhibitor with a MEK inhibitor has been associated with less skin toxicity, although the safety and efficacy of this combination are not well understood. In an article published in JCO Precision Oncology, researchers reported on the safety and efficacy of MEK and BRAF inhibition in patients with BRAF V600/NRAS Q61 wild-type melanoma. Gil Awada, MD, PhD, of the Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, and colleagues found that this combination targeted therapy resulted in the mitigation of skin toxicity and demonstrated effective antitumor activity.
A total of 24 patients with advanced BRAF V600/NRAS Q61 wild-type, immune checkpoint inhibitor–refractory melanoma were included in this phase II clinical trial (ClinicalTrials.gov identifier NCT04059224). Patients received trametinib (2 mg once daily) along with low-dose dabrafenib (50 mg twice daily) for treatment of skin toxicity. The primary study outcome was confirmed objective response rate, and the secondary outcomes included duration of response, progression-free and overall survival (time between treatment initiation and death), and incidence and severity of adverse events.
A total of seven confirmed partial responses and one unconfirmed partial response were observed (29.2%). The median duration of response was 16.6 weeks (95% confidence interval [CI] = 5.5–27.7 weeks). Additionally, stable disease was reported in five patients, and genetic alterations causing mitogen-activated protein kinase (MAPK) pathway activation were documented in six patients. The disease control rate in patients with MAPK pathway–activating alterations was 64.3%. The median progression-free survival was 13.3 weeks (95% CI = 3.5–23.1 weeks), and the median overall survival was 54.3 weeks (95% CI = 37.9–70.6 weeks). Further, serious adverse events were observed in 25% of patients.
Disclosure: For full disclosures of the study authors, visit ascopubs.org.
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