{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T22:50:11Z","timestamp":1791931811682,"version":"4.3.4"},"reference-count":38,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2019,10,4]],"date-time":"2019-10-04T00:00:00Z","timestamp":1570147200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["acsjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer"],"published-print":{"date-parts":[[2020,1]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Patients with metastatic melanoma have variable responses to combination ipilimumab and nivolumab. The objectives of this study were to examine the patterns of response and survival in patients treated with combination ipilimumab and anti\u2013PD\u20101 therapy (IPI\u00a0+\u00a0PD1) and to explore the nature of pseudoprogression and acquired resistance.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Patients with metastatic melanoma who received treatment with first\u2010line IPI\u00a0+\u00a0PD1 had all metastases \u22655\u00a0mm measured on computed tomography\/magnetic resonance imaging studies. The lesional response rate (LRR) and the overall response rate (ORR) were determined according to Response Evaluation Criteria in Solid Tumors, version 1.1.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In total, 140 patients who had 833 metastases were studied. The ORR and the overall complete response (CR) rate decreased as tumor burden or the number of metastases increased. Metastases that had a CR (49%) were smaller than metastases without a CR (median, 13 vs 17\u00a0mm; <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a0.0001). Soft\u2010tissue and lung metastases had the highest LRR (79% and 77%, respectively), whereas liver metastases had the lowest (46%). In multivariate analysis, patients with lung metastases had superior ORR (odds ratio [OR], 2.75; <jats:italic>P<\/jats:italic>\u00a0=\u00a0.02) and progression\u2010free survival (hazard ratio [HR], 0.46; <jats:italic>P<\/jats:italic>\u00a0=\u00a0.02), whereas those with liver metastases had inferior ORR (OR, 0.33; <jats:italic>P<\/jats:italic>\u00a0=\u00a0.02), progression\u2010free survival (HR, 4.03; <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a0.01), and overall survival (HR, 3.17; <jats:italic>P<\/jats:italic>\u00a0=\u00a0.01). Pseudoprogression occurred in one\u2010third of patients who had progressive disease as their best response, with an overall survival that was comparable to that of patients without disease progression. Acquired resistance occurred in 12% of responders after a median of 9.6\u00a0months, with an overall survival rate of 83% at 1\u00a0year from progression.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Metastases in different anatomical locations display distinct response patterns and also are associated with overall response and survival with combination immunotherapy. Specific sites of disease may hold unique mechanisms of resistance and should allow for more personalized treatment.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cncr.32522","type":"journal-article","created":{"date-parts":[[2019,10,4]],"date-time":"2019-10-04T09:00:31Z","timestamp":1570179631000},"page":"86-97","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":149,"title":["Site\u2010specific response patterns, pseudoprogression, and acquired resistance in patients with melanoma treated with ipilimumab combined with anti\u2013PD\u20101 therapy"],"prefix":"10.1002","volume":"126","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3540-8906","authenticated-orcid":false,"given":"Ines","family":"Pires da Silva","sequence":"first","affiliation":[{"name":"Melanoma Institute Australia Sydney New South Wales Australia"},{"name":"Central Clinical School The University of Sydney Sydney New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Serigne","family":"Lo","sequence":"additional","affiliation":[{"name":"Melanoma Institute Australia Sydney New South Wales Australia"},{"name":"Central Clinical School The University of Sydney Sydney New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camelia","family":"Quek","sequence":"additional","affiliation":[{"name":"Melanoma Institute Australia Sydney New South Wales Australia"},{"name":"Central Clinical School The University of Sydney Sydney New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Gonzalez","sequence":"additional","affiliation":[{"name":"Melanoma Institute Australia Sydney New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matteo S.","family":"Carlino","sequence":"additional","affiliation":[{"name":"Melanoma Institute Australia Sydney New South Wales Australia"},{"name":"Western Clinical School The University of Sydney Sydney New South Wales Australia"},{"name":"Department of Medical Oncology Westmead and Blacktown Hospitals Sydney New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georgina V.","family":"Long","sequence":"additional","affiliation":[{"name":"Melanoma Institute Australia Sydney New South Wales Australia"},{"name":"Department of Medical Oncology Royal North Shore and Mater Hospitals Sydney New South Wales Australia"},{"name":"Northern Clinical School The University of Sydney Sydney New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander M.","family":"Menzies","sequence":"additional","affiliation":[{"name":"Melanoma Institute Australia Sydney New South Wales Australia"},{"name":"Department of Medical Oncology Royal North Shore and Mater Hospitals Sydney New South Wales Australia"},{"name":"Northern Clinical School The University of Sydney Sydney New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,10,4]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2014.56.2736"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1709684"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(17)31601-X"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1003466"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1504030"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(18)30700-9"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc.2016.2"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0085004"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-13-3122"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/pcmr.12675"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-12-0530"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(18)30139-6"},{"key":"e_1_2_8_14_1","unstructured":"Bristol\u2010Myers Squibb. Nivolumab Combined With Ipilimumab Followed by Nivolumab Monotherapy as First\u2010Line Treatment for Patients With Advanced Melanoma (CheckMate 401). Clinicaltrials.gov identifier: NCT02599402. Accessed September 12 2019.https:\/\/clinicaltrials.gov\/ct2\/show\/NCT02599402."},{"key":"e_1_2_8_15_1","unstructured":"Bristol\u2010Myers Squibb. A Study of Two Different Dose Combinations of Nivolumab in Combination With Ipilimumab in Subjects with Previously Untreated Unresectable or Metastatic Melanoma. Clinicaltrials.gov identifier: NCT02714218. Accessed September 12 2019.https:\/\/clinicaltrials.gov\/ct2\/show\/NCT02714218."},{"key":"e_1_2_8_16_1","unstructured":"Bristol\u2010Myers Squibb. A Safety and Efficacy Study of Multiple Administration Regimens for Nivolumab Plus Ipilimumab in Subjects with Melanoma. Clinicaltrials.gov identifier: NCT02905266. 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