A new drug, dabrafenib, shows improvements over chemotherapy for patients suffering from a form of advanced skin cancer, according to the results of a Phase III study (“BREAK-3” trial) published in the Lancet.

The drug was used to treat patients suffering from a form of advanced skin cancer, known as BRAF mutation-positive melanoma, and works by blocking a key signaling protein.

Estimates suggest that there were approximately 46,000 deaths from melanoma in 2008, and while not all types of melanoma are suitable for treatment with dabrafenib, approximately 50% of melanomas carry the mutated form of the BRAF gene that allows the drug to work.

An international group of researchers, led by Dr Axel Hauschild of the Department of Dermatology, Schleswig-Holstein University Hospital in Kiel, Germany, compared dabrafenib’s performance to the most commonly used existing treatment, dacarbazine (DTIC), in 250 patients suffering from spreading or inoperable BRAF-positive melanoma. 50% of the patients demonstrated a partial (47%) or complete response (3%) to the treatment in an independent review.

By comparison, just 6% of patients treated with DTIC showed an improvement. Progression-free survival was also improved by the new drug, with the group of patients who received dabrafenib experiencing an average (median) progression-free survival time of 5.1 months, as compared to 2.7 months when treated with DTIC.

While dabrafenib is not the first drug of its kind, the new results suggest that it seems to have similar treatment efficacy and may have some advantages over the existing BRAF inhibitor, vemurafenib, which was recently approved by the US Food and Drug Administration (FDA) and the European Medicines Agency.

In particular, the results suggest that the side effects of dabrafenib affecting the skin are less severe than those experienced by patients who are treated with vemurafenib, with the researchers noting that very few of the patients in this trial experienced serious side effects.

The small number of patient deaths over the course of the dabrafenib trial meant that the researchers were unable to assess the drug’s effect on overall survival rates.

In the light of good response and progression-free survival rates from a previous phase-2 trial (“BREAK-2”), patients with progressive disease under conventional DTIC treatment were allowed to receive dabrafenib, too.

This cross-over design of the BREAK-3 trial may confound any conclusions on dabrafenib´s overall survival benefits.

Commenting on the paper, Dr Hauschild said: “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”.

Commenting on the paper, Professor Kim Margolin of the University of Washington said: “[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”.


Source: The Lancet