Overall survival data from COMBI-d trial of Mekinist + Tafinlar for Metastatic Melanoma- GSK

GlaxoSmithKline plc announced overall survival (OS) results from COMBI-d trial which demonstrate a statistically significant reduction in the risk of death (Hazard Ratio [HR] 0.71 [95% Confidence Interval (CI): 0.55, 0.92], p=0.011) for the combination of dabrafenib (Tafinlar) and trametinib (Mekinist) compared to dabrafenib monotherapy in patients with BRAF V600E/K mutation-positive Metastatic Melanoma.

The safety profile was consistent with the profile observed to date for the combination; no new safety concerns were observed.Completion of this study is a post-marketing requirement for the FDA�s Accelerated Approval for the combination in the USA.

Previous analyses from the August 2013 data cut for COMBI-d showed that treatment with the combination resulted in a 25 per cent reduction in the risk of disease progression and/or death compared to dabrafenib alone (HR 0.75 [95% CI: 0.57, 0.99], p=0.035) as assessed by investigators. The median PFS was 9.3 months in patients treated with the combination compared to 8.8 months in patients treated with dabrafenib alone. Interim OS results were previously presented, the OS data announced today is the final, planned statistical analysis. At the time of the primary analysis, the most common adverse events (?20%) for the combination arm were pyrexia, fatigue, headache, nausea, chills, joint pain (athralgia), diarrhoea, rash, hypertension and vomiting. More patients had AEs leading to dose modifications with combination arm compared to dabrafenib monotherapy. Increased incidence (51% vs 28%) and severity (grade 3, 6% vs 2%) of pyrexia occurred with combination. Increased incidence of hyperkeratosis (32% vs 3%) occurred with dabrafenib monotherapy.