Melanoma is a heterogeneous skin tumor, characterized by mutations of different oncogenes.
Almost half of patients with advanced melanoma have a gene mutation of BRAF serine-threonine
kinase. Over the past 5 years, two BRAF inhibitors targeting these mutations, vemurafenib and
dabrafenib, have shown high rates of rapid response in phase II and III studies. However, the
duration of responses is limited in most patients due to the development of acquired
resistance. Mechanisms of resistance to BRAF inhibitor therapy are diverse and include the
reactivation of the mitogen-activated protein kinase (MAPK) pathway in over two-thirds of
tumors, along with promotion of parallel signaling networks.
Recently, the combination of drugs was superior in terms of responses, Progression Free
Survival (PFS) and Overall Survival (OS) compared to monotherapy.
The data from recent studies confirm the clinical benefit of the combination of Vemurafenib
with cobimetinib and support the use of the combination as a standard first-line approach to
improve survival in patients.
The aim of this randomized, open-label, phase II study is to evaluate the efficacy, in terms
of overall survival, of vemurafenib combined with cobimetinib associated with local treatment
compared with second-line therapy, in patients with BRAFV600 mutation-positive metastatic
melanoma in focal progression with first-line combined vemurafenib and cobimetinib.