Abstract Lessons Learned The combination of trametinib and sorafenib has an acceptable
safety profile, albeit at doses lower than approved for monotherapy. Maximum tolerated
dose is trametinib 1.5 mg daily and sorafenib 200 mg twice daily. The limited anticancer
activity observed in this unselected patient population does not support further exploration of
trametinib plus sorafenib in patients with hepatocellular carcinoma. Background The
RAS/RAF/MEK/ERK signaling pathway is associated with proliferation and progression of …

TPS469 Background: MEK inhibitors have demonstrated preclinical activity in hepatocellular
carcinoma (HCC). More importantly, in xenograft models, this class of inhibitors acts
synergistically with sorafenib to inhibit tumor growth, prevent metastatic spread and increase
survival. In preclinical models, sorafenib leads to overactivation of the MAPK pathway, which
can be counterbalanced by the use of MEK inhibitors. Trametinib is a reversible, highly
selective, allosteric MEK inhibitor. Methods: This is an open label, single group, phase I …