The drug dabrafenib significantly improved progression-free survival in persons with BRAF-mutation-positive metastatic melanoma in a phase 3 trial comparing the agent with dacarbazine (DTIC), the most commonly used existing treatment.
As an inhibitor of mutated BRAF, dabrafenib is not the first drug of its kind, but the new results suggest that it may have some treatment advantages over the existing BRAF inhibitor, vemurafenib (Zelboraf), such as less severe side effects affecting the skin.
In the study, 187 persons aged 18 years and older with previously untreated, stage IV, or inoperable stage III BRAFV600E mutation-positive melanoma were randomly assigned to receive oral 150-mg doses of dabrafenib twice daily. Another 63 such patients were randomized to dacarbazine, delivered intravenously every 3 weeks in doses of 1,000 mg/m2. Patients were enrolled in the trial between December 2010 and September 2011; the investigators, led by Axel Hauschild, MD, of Schleswig-Holstein University Hospital in Kiel, Germany, used December 19, 2011, as the data cutoff point for their report, published by The Lancet.
Median progression-free survival was 5.1 months for the dabrafenib users and 2.7 months for those on dacarbazine. At data cutoff, 107 (57%) members of the dabrafenib group and 14 (22%) members of the dacarbazine group remained on randomized treatment.
Treatment-related adverse events of grade 2 or higher occurred in 100 (53%) of the 187 patients on dabrafenib and 26 (44%) of 59 remaining patients receiving dacarbazine. The most common adverse events in the dabrafenib group were skin-related toxic effects, fever, fatigue, arthralgia, and headache, whereas the dacarbazine users primarily suffered from nausea, vomiting, neutropenia, fatigue, and asthenia. Adverse events of grade 3 or grade 4 were uncommon in both groups.