A phase III study of the combination of Tafinlar ( Dabrafenib ) and Mekinist ( Trametinib ), compared to single agent therapy with Dabrafenib in patients with BRAF V600 E or K mutation positive unresectable or metastatic melanoma, met its primary endpoint of Progression Free Survival ( PFS ) ( p less than 0.05 ).
In this phase III study, progression-free survival observed among patients in the single agent Dabrafenib arm was greater than that seen in previous single agent Dabrafenib studies, leading to a more modest difference in progression-free survival between treatment arms than was observed in the phase I/II study.
In the combination arm, the most commonly reported ( greater than 20% ) adverse events were pyrexia, fatigue, nausea, headache, chills, diarrhoea, arthralgia, rash, hypertension, and vomiting.
The phase III programme for Dabrafenib and Trametinib in BRAF V600E/K metastatic melanoma comprises two studies: COMBI-d ( also known as MEK MEK115306 ) and COMBI-v ( also known as MEK116513 ).
The results are from COMBI-d, a phase III, randomised, double-blinded study comparing the combination of the BRAF inhibitor, Dabrafenib and the MEK inhibitor, Trametinib to Dabrafenib and placebo as first-line therapy in patients with unresectable ( stage IIIC ) or metastatic ( stage IV ) BRAF V600E/K mutation-positive cutaneous melanoma.
The primary endpoint of the study is progression-free survival and patients will be followed for overall survival.
The study randomised 423 patients from investigative sites in Australia, Europe, North and South America.
COMBI-v is a phase III, randomised, open-label study comparing the combination of the BRAF inhibitor, Dabrafenib and the MEK inhibitor, Trametinib to the BRAF inhibitor Vemurafenib in patients with unresectable ( stage IIIC ) or metastatic ( stage IV ) BRAF V600E/K mutation-positive cutaneous melanoma.
The primary endpoint of the study is overall survival. ( Xagena )
Source: GSK, 2014