Pembrolizumab and nivolumab: PD-1 inhibitors for advanced melanoma

Purpose. The immunology of programmed cell death protein 1 (PD-1) inhibitors, as well as the clinical efficacy of pembrolizumab and nivolumab in the treatment of metastatic melanoma, is reviewed. Summary. PD-1 inhibitors pembrolizumab and nivolumab are novel immunotherapies that were recently approved by the Food and Drug Administration for the treatment of unresectable or metastatic melanoma in treatment-refractory patients. Pembrolizumab and nivolumab are monoclonal antibodies that bind to the PD-1 receptor and prevent its interaction with its ligands programmed cell death receptor ligands 1 and 2. Inhibition of the PD-1 receptor allows for increased immune response and potentially increased anticancer immune activity. Clinical trials with pembrolizumab and nivolumab in patients with unresectable melanoma refractory to ipilimumab or targeted agents demonstrated objective response rates of 26-38% and 31-40%, respectively, and acceptable toxicity profiles. While most patients experienced some form of treatment-related adverse event, most of these effects were mild (grade 1 or 2) and were managed with treatment interruption or supportive care. Pembrolizumab is administered via continuous i.v. infusion over 30 minutes at a dose of 2 mg/kg of actual body weight every three weeks. Nivolumab is administered as a continuous i.v. infusion over 60 minutes. The recommended dose of nivolumab is 3 mg/kg of actual body weight administered every two weeks until disease progression or the development of intolerable toxicities. Conclusion. Pembrolizumab and nivolumab monotherapies are effective therapies in ipilimumab-refractory metastatic melanoma and present an overall favorable toxicity profile.