pimasertib + gemcitabine

Pimasertib + gemcitabine is a combination therapy of two small molecule drugs investigated for use in patients with metastatic pancreatic adenocarcinoma. Pimasertib is a selective, orally bioavailable, allosteric inhibitor of mitogen-activated protein kinase kinases 1 and 2 (MEK1/2); gemcitabine is a nucleoside analog that inhibits DNA synthesis. The rationale behind combining these agents is that MEK pathway inhibition by pimasertib may sensitize tumor cells to the cytotoxic effects of gemcitabine, as the MAPK/ERK pathway is frequently activated in pancreatic cancer. However, multiple phase I/II randomized studies found the combination had no clinically meaningful efficacy advantage compared to gemcitabine alone in this setting, and increased the incidence of some toxicities, notably ocular events and thrombocytopenia. The regimen has not advanced to regulatory approval for pancreatic cancer[1][4][6].