title: Current status and future directions of the immune checkpoint inhibitors ipilimumab, pembrolizumab, and nivolumab in oncology.
abstract: OBJECTIVE
  To provide the clinician with an update and the current status and future direction of approved immune checkpoint inhibitors (ICIs) in oncology.
  
  
  METHODS
  A PubMed search from January 1, 1966 to March 13, 2015 was performed using the key terms ipilimumab, pembrolizumab, lambrolizumab, nivolumab, immune checkpoint inhibitor, MDX-010, MDX-101, BMS-734016, MK-3475, SCH 900475, MDX-1106, BMS-936558, ONO-4538, CTLA-4, PD-1, or PD-L1 and cancer, oncology, or neoplasm. Additional references were identified from the investigators(') personal files, recent oncology meetings, review articles, clinical guidelines, and package inserts.
  
  
  METHODS
  All English-language clinical trials assessing the safety and efficacy of ipilimumab, nivolumab, and pembrolizumab in cancer were considered. The PubMed search resulted in 215 trials; 33 met inclusion criteria. A further 28 trials were identified from the above sources; 61 trials from 2005 to 2015 were included. We consolidated and clarified treatment recommendations for the management of immune-related adverse events (irAEs), assessed response criteria, and calculated the clinical utility of leading tumor profiling options.
  
  
  RESULTS
  Ipilimumab and nivolumab, but not pembrolizumab, have an overall survival (OS) advantage over chemotherapy first line in unresectable/metastatic melanoma. Nivolumab has an OS advantage versus chemotherapy in second-line squamous non-small-cell lung cancer. Data in other settings are promising. Nivolumab and pembrolizumab are better tolerated than ipilimumab. Further validation of response criteria is needed. Tumor profiling to predict clinical benefit is premature but promising.
  
  
  CONCLUSIONS
  The treatment landscape in oncology is quickly evolving with the advent of ICIs.
authors.affiliation: Memorial Sloan Kettering Cancer Center, New York, NY, USA.
authors.forename: Meagan S
authors.initials: MS
authors.lastname: Barbee
authors.affiliation: Memorial Sloan Kettering Cancer Center, New York, NY, USA.
authors.forename: Adebayo
authors.initials: A
authors.lastname: Ogunniyi
authors.affiliation: Memorial Sloan Kettering Cancer Center, New York, NY, USA.
authors.forename: Troy Z
authors.initials: TZ
authors.lastname: Horvat
authors.affiliation: Memorial Sloan Kettering Cancer Center, New York, NY, USA dangt@mskcc.org.
authors.forename: Thu-Oanh
authors.initials: TO
authors.lastname: Dang
mesh_terms: D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D059447:Cell Cycle Checkpoints / Q000187:drug effects*; D006801:Humans; D000074324:Ipilimumab; D009369:Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D000077594:Nivolumab
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D000074324:Ipilimumab; D000077594:Nivolumab; C582435:pembrolizumab
keywords: CTLA-4; PD-1; immune checkpoint inhibitor; ipilimumab; nivolumab; pembrolizumab