Pre-surgical targeted therapy is feasible and well-tolerated in patients with advanced BRAF mutation-positive melanoma, according to a recent study published in the Journal of the American College of Surgeons.
Adam Johnson, MD, and colleagues at the Vanderbilt University Medical Center in Nashville, TN, looked at 12 patients with locally or regionally advanced BRAF mutation-positive melanoma who received preoperative dabrafenib for 14 days followed by dabrafenib with trametinib for 14 days prior to surgery. They measured biopsies and tumor size at baseline, as well as at days 14 and 28.
The researchers found that therapy was well-tolerated, with toxicity greater than grade 3 found in only two patients. All patients had a substantial reduction in tumor volume, with 65 percent reduction at day 14 and 78 percent at day 28, as well as a marked reduction in viable melanoma cells at 14 days of dabrafenib therapy.
In addition, proliferation of residual melanoma cells was reduced while apoptosis was increased.
“Further investigation of the anti-tumor immune response during targeted therapy and the mechanisms of intrinsic resistance may yield novel therapeutic strategies,” the authors concluded.
In this study the authors conducted a prospective trial of BRAF and MEK targeted therapy in advanced, operable BRAF mutation-positive melanoma to determine feasibility, tumor response rates and biomarkers of response and resistance.