Updated analysis confirmed improvement in overall survival with the combination of dabrafenib and trametinib, compared with vemurafenib alone, in patients with unresectable or metastatic cutaneous melanoma that expresses BRAF V600/K mutation, according to a study presented here at the 2015 European Cancer Congress (ECC).
The median overall survival in patients receiving the combination therapy was 25.6 months versus 18 months for patients receiving vemurafenib (P < .001).
At 2 years, 51% of the patients who were treated with dabrafenib plus trametinib remained alive compared with 38% of the patients on vemurafenib.
"Dabrafenib plus trametinib has demonstrated superiority over BRAF inhibitor monotherapy in 2 phase 3 trials, supporting its use as a standard of care therapy in patients with BRAF V600-mutant melanoma," said Caroline Robert, MD, Institute Gustave Roussy, Paris, France.
The researchers enrolled 704 patients with Stage IIIC or Stage IV cutaneous BRAF V600-mutant melanoma. To be eligible for the trial the patients had to be free of brain metastases unless those metastases were treated and their condition has to have been stable for at least 12 weeks. All patients had an ECOG performance status of 0-1. Patients were randomised to receive dabrafenib 150 mg twice daily plus trametinib 2 mg once daily (n = 352) or vemurafenib 960 mg twice daily (n = 352).
The trial was ended in April 2014 when the independent data monitoring committee recommended stopping the trial for efficacy.
The researchers also evaluated outcome on the basis of the level of lactate dehydrogenase (LDH), a marker of tissue damage. The patients were stratified on the basis if the level was greater or lesser than the upper limits of normal. Among patients with higher levels of LDH, the median overall survival was 21.5 months, but after 2 years, the median overall survival among patients with low LDH levels has not yet been reached.
"The updated results show that the combination of dabrafenib plus trametinib improved overall survival versus vemurafenib, improved progression-free survival, improved the overall response rate, and improved the duration of response," said Dr. Robert.