9068 Background: Inhibitors of mutant BRAF have transformed the treatment of melanoma for the 40% of patients whose tumors harbor V600 mutations. ERK1/2 is constitutively active in melanoma cells regardless of mutation status, and plays key roles in cell cycle entry, invasion, angiogenesis and in resistance to apoptosis. Selumetinib is a highly selective allosteric inhibitor of MEK1/2, suppressing pERK levels in melanoma independent of BRAF and NRAS mutation status. In melanoma cells, docetaxel induces mitochondrial dependent apoptosis by activation of Bax. Activation of ERK1/2 results in degradation of the BH3-only protein Bim and phosphorylation of Bad, inhibiting apoptosis. Selumetinib and docetaxel have demonstrated synergy in a variety of xenograft models, including melanoma. Methods: DOC-MEK (NCT01256359) is a randomised, double-blind, placebo-controlled multi-centre study in patients with wild-type BRAF advanced melanoma. Patients were randomised (1:1) to docetaxel with placebo or selumetinib, with...