title: Ipilimumab Combined with Nivolumab: A Standard of Care for the Treatment of Advanced Melanoma?
abstract: Ipilimumab, an inhibitor of CTLA-4 on T cells, was the first drug to improve overall survival in patients with advanced melanoma. Subsequently, inhibitors of PD-1, including nivolumab and pembrolizumab, were shown to be superior to ipilimumab with a more favorable safety profile. The combination of ipilimumab and nivolumab is associated with a further improvement in response rate and progression-free survival; however, the combination is associated with an increased rate of immune-related toxicities. In 2015, the FDA approved the combination for the treatment of BRAF wild-type advanced melanoma. This review examines the preclinical rationale for the combination of ipilimumab and nivolumab as well as the efficacy and toxicity data from clinical trials in patients with advanced melanoma. Finally, alternative treatment options are discussed with a focus on patient selection. Clin Cancer Res; 22(16); 3992-8. ©2016 AACR.
authors.affiliation: Melanoma Institute Australia, The University of Sydney, and Crown Princess Mary Cancer Centre, Westmead and Blacktown Hospitals, Sydney, Australia.
authors.forename: Matteo S
authors.initials: MS
authors.lastname: Carlino
authors.affiliation: Melanoma Institute Australia, The University of Sydney, and Royal North Shore and Mater Hospitals, Sydney, Australia. georgina.long@sydney.edu.au.
authors.forename: Georgina V
authors.initials: GV
authors.lastname: Long
mesh_terms: D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D014408:Biomarkers, Tumor; D060908:CTLA-4 Antigen / Q000037:antagonists & inhibitors; D002986:Clinical Trials as Topic; D006801:Humans; D000074324:Ipilimumab / Q000008:administration & dosage; D008545:Melanoma / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality; D058990:Molecular Targeted Therapy; D000077594:Nivolumab; D018579:Patient Selection; D061026:Programmed Cell Death 1 Receptor / Q000037:antagonists & inhibitors; D059039:Standard of Care; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D014408:Biomarkers, Tumor; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D000074324:Ipilimumab; D061026:Programmed Cell Death 1 Receptor; D000077594:Nivolumab