Metastatic melanoma has a poor prognosis with a median survival for patients with stage IV melanoma ranging from 6 to 9 months and a 3-year survival rate of only 10-15%. Generally, metastatic melanoma is difficult to treat, because advanced melanomas are refractory to most standard systemic therapies and therapeutic options are limited.

Vemurafenib, a kinase which also inhibits the BRAF V600E mutation, is one in a series of BRAF-kinase inhibitors and is indicated for patients with BRAF V600E mutation positive advanced/metastatic unresectable melanoma. It is currently not approved by the EMA, but approval was recommended by the Committee for Medicinal Products for Human Use of EMA as first-in-class treatment for metastatic or unresectable melanoma in December 2011. The approval is expected in February 2012. In the US, the FDA granted market authorization based on the (ongoing) BRIM-3 study in August 2011.

The BRIM-3 study, a phase III trial, evaluated vemurafenib in comparison to dacarbazine, in previously untreated patients. Improved results for progression-free survival (i.e. a gain of 3.7 months for patients treated with vemurafenib), were found, but no reliable OS data are available, since cross-over was allowed after an interim-analysis. About one third of patients treated with vemurafenib develop – as a side effect – squamous cell carcinoma of the skin.
The assessment was carried out in collaboration with the Italian Horizon Scanning project ULSS 20.