Immunotherapies and novel combinations: the focus of advances in the treatment of melanoma

Abstract

Since 2011, the approval of four different classes of novel drugs (the anti-CTLA-4 agent, ipilimumab; BRAF inhibitors [BRAFi]; MEK inhibitors [MEKi]; and the anti-PD-1 drug, pembrolizumab) has revolutionized the care of advanced melanoma, with the disease becoming a model for the development of new treatments for other types of cancer. Further advances in the treatment of melanoma represented some of the key highlights of the European Society of Medical Oncology (ESMO) 2014 congress. The first phase III trial of an anti-PD-1 agent to report the CA209-037 study included 405 patients with metastatic melanoma previously treated with ipilimumab who were randomized 2:1 to receive nivolumab 3 mg/kg every 2 weeks or investigator’s choice chemotherapy. Nivolumab was associated with a higher response rate than chemotherapy and was well tolerated, with adverse events mostly low grade and manageable using recommended treatment algorithms. New data on other immunotherapies, namely ipilimumab and pembrolizumab, were also reported. In addition, outside of immunotherapy, combination approaches involving targeted agents were also a major focus of ESMO this year, with two major phase III studies of combined BRAF inhibition and MEK inhibition being reported. Overall, new clinical trial findings reported at ESMO further endorse the view that melanoma, given the continued development of novel, effective compounds, can accurately be described as the most “dynamic” field of oncology at present.