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However, there was some heterogeneity as well as some variation in the degree of benefit across studies. We reviewed randomized trials and performed a meta\u2010analysis to determine the efficacy and safety of immune checkpoint inhibitors in comparison with conventional regimens. Eligible studies were limited to randomized controlled trials comparing anti\u2010CTLA\u20104 or anti\u2010PD\u20101 inhibitors to chemotherapy or vaccination treatment in adult patients with unresectable cutaneous metastatic melanoma. Progression\u2010free survival (PFS) rate at 6\u00a0months was 28.5% versus 17.7% (RR: 0.84, 95% CI: 0.76\u20130.93), overall survival (OS) rate at 1\u00a0year was 51.2% versus 38.8% (RR: 0.72, 95% CI: 0.59\u20130.88), and overall response rate (ORR) at 6\u00a0months was 29.6% versus 17.7% (RR: 0.85, 95% CI: 0.76\u20130.95) favoring immune check point inhibitors over chemotherapies or vaccination. Immune check point inhibitors were associated with more frequent immune\u2010related adverse events at 13.7% versus 2.4% of treated patients (RR: 6.74, 95% CI: 4.65\u20139.75). Subgroup analyses demonstrated significant PFS (RR: 0.92 vs. 0.74, <jats:italic>P\u00a0<\/jats:italic>&lt;<jats:italic>\u00a0<\/jats:italic>0.00001) and ORR (RR: 0.95 vs. 0.76, <jats:italic>P\u00a0<\/jats:italic>=<jats:italic>\u00a0<\/jats:italic>0.0004) improvement with anti\u2010PD\u20101 treatment compared to anti\u2010CTLA\u20104 when each of them was compared to control treatments. Collectively, these results demonstrate that immune checkpoint inhibitors have superior outcomes compared to conventional chemotherapies or vaccination, and support the results of recent randomized trials that showed superior outcomes with anti\u2010PD\u20101 agents over ipilimumab in unresectable metastatic cutaneous melanoma patients.<\/jats:p>","DOI":"10.1002\/cam4.732","type":"journal-article","created":{"date-parts":[[2016,5,11]],"date-time":"2016-05-11T06:29:44Z","timestamp":1462948184000},"page":"1481-1491","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":89,"title":["Targeting immune checkpoints in unresectable metastatic cutaneous melanoma: a systematic review and meta\u2010analysis of anti\u2010CTLA\u20104 and anti\u2010PD\u20101 agents trials"],"prefix":"10.1002","volume":"5","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7343-1635","authenticated-orcid":false,"given":"Seongseok","family":"Yun","sequence":"first","affiliation":[{"name":"Department of Medicine University of Arizona  Tucson Arizona 85721"},{"name":"Hematology and Oncology University of Arizona  Tucson Arizona 85721"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole D.","family":"Vincelette","sequence":"additional","affiliation":[{"name":"Molecular Pharmacology and Experimental Therapeutics Mayo Clinic  Rochester Minnesota 55905"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Myke R.","family":"Green","sequence":"additional","affiliation":[{"name":"Hematology and Oncology University of Arizona  Tucson Arizona 85721"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea E.","family":"Wahner Hendrickson","sequence":"additional","affiliation":[{"name":"Medical Oncology Mayo Clinic  Rochester Minnesota 55905"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivo","family":"Abraham","sequence":"additional","affiliation":[{"name":"Center for Health Outcomes and PharmacoEconomic Research University of Arizona  Tucson Arizona 85721"},{"name":"Arizona Cancer Center University of Arizona  Tucson Arizona 85721"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2016,5,11]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1103782"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1406037"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(12)70431-X"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(14)70012-9"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.271.5256.1734"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc3239"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2012.44.6112"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm730"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.2762"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0915174107"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2013.53.0105"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(15)70076-8"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2013.51.4802"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(14)60958-2"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jclinepi.2009.06.005"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1136\/postgradmedj-2015-133535"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1097\/CJI.0b013e31823735d6"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.28620"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1305133"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1200690"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1302369"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(09)70334-1"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10637-009-9376-8"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-09-1024"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdq013"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2014.13943"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1186\/1479-5876-12-116"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1186\/1756-9966-33-30"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(12)70324-8"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdu577"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2009.26.7609"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2008.16.1927"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1245\/ASO.2005.03.536"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.3109\/07357907.2014.885984"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(15)70122-1"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2014.56.6018"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdt291"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.2013.298"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdu441"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdt161"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-11-1823"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1186\/1479-5876-13-S1-O5"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1104621"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1003466"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1412082"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(15)00083-2"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2009.23.4799"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.1995.03530220066035"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1097\/PRS.0b013e318219c171"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1503093"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1504030"},{"key":"e_1_2_8_53_1","unstructured":"NCCN 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