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The first monoclonal antibodies against the immune checkpoint programmed death 1 (<jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content>\u20101) receptor, nivolumab and pembrolizumab, are now approved for clinical use. Both agents are indicated for the treatment of advanced melanoma, as well as for the treatment of metastatic non\u2013small cell lung cancer (<jats:styled-content style=\"fixed-case\">NSCLC<\/jats:styled-content>). Nivolumab is also approved for the treatment of advanced renal cell carcinoma. In patients with melanoma, these agents result in objective response rates of ~25\u201340%, with durable responses lasting more than 2\u00a0years in some cases. Results from phase <jats:styled-content style=\"fixed-case\">III<\/jats:styled-content> trials have shown improved survival with nivolumab versus standard\u2010of\u2010care chemotherapy in both patients with advanced melanoma and those with advanced <jats:styled-content style=\"fixed-case\">NSCLC<\/jats:styled-content>. In patients with advanced melanoma, both <jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content>\u20101 inhibitors (nivolumab and pembrolizumab) have shown improved survival versus ipilimumab. <jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content>\u20101 inhibitors are associated with adverse events that have immune etiologies, with grade greater than 3 adverse events typically reported in 16% or less of patients. However, most immune\u2010mediated adverse events (including grade 3\u20134 adverse events) can be managed by using published management algorithms without permanent discontinuation of the agent. As nivolumab and pembrolizumab enter the clinic, and with more <jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content>\u20101 pathway agents in development for a range of tumor types, this review aims to provide pharmacists with a basic understanding of the role of <jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content>\u20101 in modulating the immune system and their use in the cancer treatment. The most recent clinical efficacy and safety data are discussed, highlighting the response characteristics distinctive to immune checkpoint inhibitors, along with pharmacokinetic and pharmacodynamic data and cost considerations.<\/jats:p>","DOI":"10.1002\/phar.1714","type":"journal-article","created":{"date-parts":[[2016,1,29]],"date-time":"2016-01-29T02:55:44Z","timestamp":1454036144000},"page":"317-334","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":75,"title":["PD\u20101 Pathway Inhibitors: Immuno\u2010Oncology Agents for Restoring Antitumor Immune Responses"],"prefix":"10.1002","volume":"36","author":[{"given":"Patrick J.","family":"Medina","sequence":"first","affiliation":[{"name":"Department of Pharmacy: Clinical and Administrative Sciences The University of Oklahoma College of Pharmacy Oklahoma City Oklahoma"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Val R.","family":"Adams","sequence":"additional","affiliation":[{"name":"Pharmacy Practice and Science Department University of Kentucky College of Pharmacy Lexington Kentucky"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2016,3,20]]},"reference":[{"key":"e_1_2_12_2_1","volume-title":"Yervoy (ipilimumab) prescribing information","year":"2015"},{"key":"e_1_2_12_3_1","volume-title":"Keytruda (pembrolizumab) prescribing information","year":"2015"},{"key":"e_1_2_12_4_1","volume-title":"Opdivo (nivolumab) prescribing information","year":"2015"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1158\/2326-6066.CIR-14-0040"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(14)60958-2"},{"key":"e_1_2_12_7_1","doi-asserted-by":"crossref","DOI":"10.1200\/jco.2015.33.15_suppl.8032","article-title":"Safety and clinical activity of MEDI4736, an anti\u2010programmed cell death\u2010ligand 1 (PD\u2010L1) antibody, in patients with non\u2010small cell lung cancer (NSCLC) [abstract 8032]","volume":"33","author":"Rizvi NA","year":"2015","journal-title":"J Clin Oncol"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature13904"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-07-4079"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc3239"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(00)00026-1"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0503726102"},{"key":"e_1_2_12_13_1","doi-asserted-by":"crossref","first-page":"5211","DOI":"10.4049\/jimmunol.163.10.5211","article-title":"Induction of tumor immunity by removing CD25+ CD4+ T cells: a common basis between tumor immunity and autoimmunity","volume":"163","author":"Shimizu J","year":"1999","journal-title":"J Immunol"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2015.03.030"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.2008.00662.x"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-13-3271"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri2326"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.seminoncol.2015.02.015"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/cmi.2010.28"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1155\/2012\/656340"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-12-1187"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1001821"},{"key":"e_1_2_12_23_1","unstructured":"U.S. Food and Drug Administration.Medical Reviewers Report Product: Proleukin (aldesleukin) Proleukin interleukin\u20102 (IL\u20102). 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