Drug therapy of melanoma: anti-CTLA-4 and anti-PD-1 antibodies

Management of patients with metastatic melanoma has improved radically in recent years with the development of new drugs capable of significantly prolonging life expectancy. Two strategies have been implemented: targeted anti-BRAF therapy for BRAF-mutated melanomas, and non specific immunotherapies based on anti-CTLA-4 (ipilimumab) and, more recently, anti-PD-1 monoclonal antibodies. These antibodies; by blocking physiological brakes on immune activation, induce an indirect immune response. Ipilimumab, a drug approved in 2011 is of benefit to 20 % of patients but can also trigger significant immune-mediated toxicity. Anti-PD-1 antibodies presently in development seem to have a better therapeutic index, with higher response rates and less toxicity than ipilimumab. Combination therapy with anti-CTLA-4 and anti-PD-1v is also giving encouraging preliminary results. In future, these new drugs will probably be used in combination, either concurrently or sequentially.