Trametinib/Dabrafenib Combo Shows Survival Benefit Versus Vemurafenib in Melanoma Patients
Phase III trial stopped early
A phase III study of the MEK inhibitor trametinib (Mekinist, GlaxoSmithKline), in combination with the BRAF inhibitor dabrafenib (Tafinlar, GlaxoSmithKline), compared with vemurafenib (Zelboraf, Genentech/Daiichi Sankyo) in patients with BRAF V600E or V600K mutation-positive unresectable or metastatic cutaneous melanoma has been stopped early on the recommendation of an independent data monitoring committee.
The recommendation was based on an interim analysis, which demonstrated an overall survival benefit for the trametinib/dabrafenib combination compared with vemurafenib that crossed the pre-specified efficacy stopping boundary. The safety profile of the trametinib/dabrafenib arm was consistent with the safety profile of the combination observed to date.
Further analysis of the safety and efficacy data is under way and will be completed in the coming months. Eligible study patients who were randomly assigned to the vemurafenib arm will be allowed to cross over to treatment with the trametinib/dabrafenib combination.
The randomised, open-label COMBI-v trial compared the combination of dabrafenib and trametinib with vemurafenib in 704 subjects with unresectable (stage IIIC) or metastatic (stage IV) BRAF V600E/K mutation-positive cutaneous melanoma.
The study’s primary objective was to evaluate dabrafenib/trametinib combination therapy compared with vemurafenib monotherapy with respect to overall survival. Secondary objectives evaluated the dabrafenib/trametinib combination versus vemurafenib with respect to progression-free survival, the overall response rate, and the duration of response.
The safety of dabrafenib/trametinib combination therapy, including incidences of squamous cell carcinoma and other proliferative skin diseases, was also evaluated.
The combination of trametinib and dabrafenib is approved for use in the U.S. in patients with unresectable or metastatic melanoma who have the BRAF V600E or V600K mutation.
Source: GlaxoSmithKline; July 17, 2014.