Abstract
Trametinib is one of the selective inhibitors of mitogen-activated kinase 1 and 2 (MEK1, MEK2). This kinase is a part of extracellular signal-regulated kinase (MAP) influencing cellular proliferation, differentiation, and transcription.
MAP kinase is permanently activated by BRAF gene mutation, most often present in malignant melanoma. Trametinib is being given orally to patients with non-resectable or metastatic (advanced) melanoma with BRAF gene mutation, both in monotherapy and in combination with BRAF inhibitor dabrafenib.
Its effectiveness has been validated in phase III multicentric randomized clinical trials (again, both for monotherapy and combination with dabrafenib). Trametinib monotherapy was compared with chemotherapy while combination therapy (trametinib plus dabrafenib) was compared with BRAF inhibitor monotherapy.
According to the available trials, trametinib - in monotherapy or combined with dabrafenib - significantly prolongs both overall survival and progression-free survival in patients with advanced melanoma. Currently, trametinib is mostly used together with dabrafenib in order to postpone the development of resistance to BRAF inhibitors.
Trametinib, especially when combined with dabrafenib, has become a crucial of new therapeutic schemes used in advanced melanoma