Systemic therapy of metastatic melanoma

Metastatic melanoma is an aggressive form of cancer characterised by poor prognosis and a complex etiology. Until 2010, the treatment options for metastatic melanoma were very limited. Largely ineffective dacarbazine, temozolamide or fotemustine were the only agents in use for 35 years. Last decade has brought significant survival improvement in patients with metastatic melanoma with targeted therapies and immuno therapies. As our understanding of the mechanisms of action of these therapeutics evolves, even more impressive therapeutic success is being achieved through various combination strategies, including combinations of different immuno therapies as well as with other modalities. In recent years, the development of molecularly targeted inhibitors in parallel with the development of checkpoint inhibition immuno therapies has rapidly improved the outcomes for metastatic melanoma patients. Despite these new therapies showing initial promise; resistance and poor duration of response have limited their effectiveness as mono therapies. Furthermore, current studies investigate the combined or sequential use of ICIs (immune checkpoint inhibitors) plus BRAF/MEK inhibitors. Combining older therapies with the new molecular and immuno therapies will be the most promising way forward for treatment of metastatic melanoma. Several studies focus particularly on poor prognosis patients, as e.g., on anti-PD-1 refractory melanoma, patients with brain metastases, or uveal melanoma. It is hoped , that these new approaches further improve long term survival in patients with advanced or metastatic melanoma. (author)