gemcitabine + erlotinib + sorafenib

This is a multi-drug oncology regimen combining the cytotoxic nucleoside analog gemcitabine with two oral targeted kinase inhibitors, erlotinib and sorafenib. Gemcitabine inhibits DNA synthesis after intracellular phosphorylation, causing S-phase arrest and apoptosis. Erlotinib is an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor that blocks EGFR signaling. Sorafenib is a multikinase inhibitor targeting RAF kinases (CRAF, BRAF) and receptor tyrosine kinases involved in angiogenesis and proliferation including VEGFR-2, VEGFR-3, and PDGFR-β. The combination was clinically explored primarily in advanced pancreatic cancer following the survival benefit seen with gemcitabine plus erlotinib; early-phase studies assessed adding sorafenib to this backbone for potential dual EGFR/VEGF-pathway blockade alongside chemotherapy. A phase II study of sorafenib with gemcitabine and erlotinib in advanced pancreatic cancer was conducted, and an ASCO abstract reported the triplet as generally tolerable; however, efficacy advantage over historical controls was not established in related doublet studies of erlotinib plus sorafenib without gemcitabine, and development of the triplet did not progress to approval. Mechanistically, the triplet combines antimetabolite cytotoxicity with EGFR pathway inhibition and multi-kinase (RAF/VEGFR/PDGFR) inhibition.

Other names

GES regimen