Targeting BRAF V600E/K mutation-positive melanoma with a combination of dabrafenib plus trametinib achieves longer overall survival and progression-free survival as well as better response rates, compared to treatment with vemurafenib alone. This data from an open-label phase III trial was presented at the European Society for Medical Oncology (ESMO) 2014 Congress in Madrid, Spain.
“We knew from previous studies of dabrafenib plus trametinib that the response rates were higher than those observed with dabrafenib monotherapy and that the progression-free survival was also significantly longer,” said lead author Caroline Robert, MD, PhD, head of Dermatology at the Institute Gustave Roussy, Paris, France.
The ongoing two-arm study has randomized 704 patients with advanced BRAF V600E/K mutation-positive melanoma either to a combination of dabrafenib (150 mg twice daily) plus trametinib (2 mg once daily), or to vemurafenib (960 mg twice daily) alone. The primary end point is overall survival, with secondary end points of progression-free survival, objective response rate, duration of response, and safety.
This preplanned interim analysis showed a 31% improvement in overall survival among patients on combination therapy, and a 44% reduction in the risk of disease progression compared to vemurafenib monotherapy. Researchers found a median progression-free survival of 11.4 months for dabrafenib plus trametinib, and 7.3 months for vemurafenib.
Patients in both arms of the study had similar rates of severe adverse events, although treatment with combination therapy was associated with a much lower rate of cutaneous squamous cell carcinoma.
In July 2014, the study was stopped, and patients originally randomized to the vemurafenib arm of the trial were allowed to cross over to the combination arm.
In summary, Robert said, “These results further corroborate the early preclinical data that more complete blockade of the MAP kinase pathway delays the emergence of resistance, translating into longer survival for the patients.”