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Combined BRAF and MEK Inhibition Offers Survival Benefit in Melanoma
A meta-analysis of 7 studies showed that combined BRAF and MEK inhibition improved survival outcomes in patients with metastatic melanoma, despite gastrointestinal toxicities (Cancer Med. 2019 Aug 8. Epub ahead of print).
“Melanoma is a potentially fatal malignancy with poor prognosis. Several recent studies have demonstrated that combination therapy of BRAF and MEK inhibition achieved better curative effect and appeared less toxic effects,” explained Qingliang Yu, MD, Guangxi Medical University, Nanning, China, and co-investigators, who compared the efficacy and safety of combining BRAF and MEK inhibition with BRAF inhibition monotherapy in melanoma.
Dr Yu and colleagues searched PubMed, EMBASE, and the Cochrane Library from June 2010 and January 2019. In total, 7 randomized controlled trials involving 3146 patients with metastatic melanoma who were diagnosed with BRAF v600E or BRAF V600K mutations, were included in the analysis.
Results showed that combined therapy with BRAF and MEK inhibition significantly improved overall survival (risk ratio (RR)=1.13; 95% CI, 1.08, 1.19; P<0.00001), progression-free survival (RR=0.57; 95% CI, 0.52, 0.63; P<0.00001), response rate (RR=1.36; 95% CI, 1.28, 1.45; P<0.00001) and mortality 0.78 (95% CI, 0.69, 0.88; P<0.0001) versus BRAF inhibition monotherapy.
Incidence of skin-related adverse events such as hyperkeratosis and cutaneous squamous-cell carcinoma was less common with combed therapy versus monotherapy, however, of gastrointestinal events including nausea, diarrhea, and vomiting were more common in the combined therapy group.
“Doublet BRAF and MEK inhibition achieved better survival outcomes over single-agent BRAF inhibition and occurred less skin-related events, but gastrointestinal events were more in combination therapy,” concluded Dr Yu and colleagues. Additional research is warranted.—Kaitlyn Manasterski
