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BRAF/MEK inhibitors safely treated patients with metastatic melanoma
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The BRAF inhibitor dabrafenib and the MEK inhibitor trametinib were safely combined at full monotherapy doses for patients with metastatic melanoma and BRAF V600 mutations, according to study results.
Researchers studied 247 patients with metastatic melanoma and BRAF V600 mutations. In parts A and B of the open-label study, 85 patients received oral dabrafenib (75 mg or 150 mg twice daily) and trametinib (1 mg, 1.5 mg or 2 mg daily). In part C, a phase 2 trial, 162 patients were divided into three groups of 54 and randomly assigned 150 mg dabrafenib twice daily plus 1 mg or 2 mg trametinib (n=54) once daily or 150 mg dabrafenib monotherapy twice daily. Incidence of cutaneous squamous cell carcinoma, survival free of melanoma progression, and response were used as primary endpoints in the phase 2 study. Overall survival and pharmacokinetic activity were secondary endpoints.
Jeffrey S. Weber
In part C, patients receiving 150 mg dabrafenib and 2 mg trametinib (combination 150/2) had dose-limiting toxic effects. Seven percent of patients receiving combination 150/2 and 19% receiving monotherapy exhibited cutaneous squamous cell carcinoma (P=.09). The 150/2 group experienced pyrexia more often than the monotherapy group (71% vs. 26%), and they showed median progression-free survival of 9.4 months compared with 5.8 months for monotherapy patients. Hazard ratio for progression or death was 0.39 (95% CI, 0.25-0.62). Combination 150/2 patients had a rate of 76% for complete or partial response, compared with 54% for the monotherapy group (P=.03).
“The combination of a BRAF plus a MEK drug can overcome resistance to BRAF inhibition, decrease toxicity of either drug alone, and prolong progression-free and possibly overall survival in stage IV melanoma patients,” researcher Jeffrey S. Weber, MD, PhD, senior member of the department of cutaneous oncology and director of the Donald A. Adam Comprehensive Melanoma Research Center, Moffitt Cancer Center in Tampa, Fla., told Healio.com. “This will be a significant, if incremental, advance in treatment for melanoma.”
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