• Lesley J Scott.
• Springer, Private Bag 65901, Mairangi Bay, 0754, Auckland, New Zealand, demail@springer.com.
• Drugs. 2015 Aug 1; 75 (12): 1413-24.

AbstractAn improved understanding of cancer genetics and immune regulatory pathways, including those associated with evasion of immune surveillance by tumours, has culminated in the development of several targeted therapies. One such strategy that acts to negate evasion of immune surveillance by tumours is inhibition of the programmed cell death receptor-1 (PD-1) checkpoint pathway. Intravenous nivolumab (Opdivo(®)), a PD-1 checkpoint inhibitor, is approved or in pre-registration in various countries for use in adult patients with advanced melanoma, with the recommended monotherapy dosage being a 60-min infusion of 3 mg/kg once every 2 weeks. In well-designed multinational trials, as monotherapy or in combination with ipilimumab (a cytotoxic T-lymphocyte antigen 4 checkpoint inhibitor), nivolumab significantly improved clinical outcomes and had a manageable tolerability profile in adult patients with advanced melanoma with or without BRAF mutations. Nivolumab monotherapy was associated with a higher objective response rate (ORR) than chemotherapy in treatment-experienced patients and a higher ORR and prolonged progression-free survival (PFS) and overall survival than dacarbazine in treatment-naive patients. In combination with ipilimumab, nivolumab was associated with an improved ORR and prolonged PFS compared with ipilimumab monotherapy in treatment-naive patients. In addition, nivolumab monotherapy significantly prolonged PFS and improved ORRs compared with ipilimumab monotherapy. The optimal combination regimen for immune checkpoint inhibitors remains to be fully elucidated, with various combination regimens and different sequences of individual immunotherapies currently being investigated in ongoing clinical trials. Given the significant improvements in outcomes associated with nivolumab in clinical trials, nivolumab monotherapy or combination therapy is a valuable first-line or subsequent treatment option for adult patients with unresectable or metastatic melanoma, irrespective of BRAF mutation status.

37 keywords...

hide…