Dabrafenib shows promise for melanoma patients

Results of the 'BREAK3 trial, a Phase III study of dabrafenib to treat patients with BRAF mutation-positive melanoma, i.e. a type of advanced skin cancer that works by inhibiting a key signaling protein, has demonstrated that these patients have better results with dabrafenib than with chemotherapy. The study has been published Online First in The Lancet. In 2008, an estimated 46,000 people died from melanoma. Dabrafenib is suitable for use in about half of all melanomas, i.e. in those that contain the mutated form of the BRAF gene. Research leader, Dr Axel Hauschild from the Kiel University Hospital's Department of Dermatology in Germany and his international team decided to compare the efficacy and safety of dabrafenib's to dacarbazine (DTIC), the most commonly used existing treatment. The trial was conducted in 250 patients with spreading or inoperable BRAF-positive melanoma. An independent review demonstrated that half of the patients had a partial (47%) or complete response (3%) to dabrafenib compared with only 6% of those treated with DTIC. The new drug also improved progression-free survival, with those in the dabrafenib group having an average progression free survival time of 5.1 months compared with 2.7 months in patients in the DTIC group. Vermurafenib is another drug recently approved the US food and Drug Administration (FDA) and the European Medicines Agency for the treatment of BRAF-mutation positive melanoma has a similar efficacy to dabrafenib. However, dabrafenib may have some advantages over vermurafenib as the findings indicate that dabrafenib's side effects on the skin are less severe than those of vermurafenib. The team also noted that patients suffered very few serious side effects in the trial. The team notes that the overall survival rates of dabrafenib could not be assessed during this trial due to the small number of patient deaths during the trial. Dabrafenib could also be used in patients with progressive disease who underwent conventional DTIC therapy, given that the drug demonstrated a good response and progression-free survival rates in the previous phase-2 trial ("BREAK-2"). The BREAK-3 trial's crossover may contradict any conclusions on dabrafenib´s overall survival benefits. Dr Hauschild concluded: "This trial is good news for our patients with metastatic melanoma. Competition in the field is appreciated since it accelerates new clinical trials, particularly in the combinational setting. This trial is a major step forward in the run for an improvement of the survival for this disease, which was thought to be untreatable for decades". Professor Kim Margolin from Washington University wrote in an associated comment: "This paper joins the rapidly growing list of classic articles in this exciting discipline, where the rewards from scientific discovery are increasing benefits for patients with melanoma".