{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T16:41:28Z","timestamp":1790700088417,"version":"4.1.0"},"reference-count":23,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2022,8,3]],"date-time":"2022-08-03T00:00:00Z","timestamp":1659484800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2023,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>In patients with advanced melanoma, immune\u2010checkpoint inhibitors (ICIs) represent the mainstay for first line treatment. Recently, relatlimab+nivolumab was proposed as a new combination therapy. This review was aimed at summarizing the current data of effectiveness for ICIs. Progression\u2010free survival (PFS) was the endpoint of our analysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>After a standard literature search, Phase II\/III studies comparing different ICI regimens in previously untreated advanced melanoma patients were analyzed. Patient\u2010level data were reconstructed from Kaplan\u2013Meier curves by application of the IPDfromKM method. These reconstructed datasets were used to perform indirect comparisons between treatments. Standard statistical testing was used, including hazard ratio and medians. A secondary analysis employed the restricted mean survival time.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Six trials were included in our analysis. Information on PFS from these trials was pooled according to the following treatments: nivolumab or pembrolizumab as monotherapy, or in combination with ipilimumab, and relatlimab\u2009+\u2009nivolumab. Pembrolizumab+ipilimumab showed significantly better PFS compared with the other treatments; nivolumab+ipilimumab ranked second; the other treatments showed a similar survival pattern.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The picture of comparative effectiveness resulting from our analysis is complex. The IPDfromKM method is advantageous because it accounts for the length of follow\u2010up but loses the balance between treatment group and controls determined by randomization. Based on indirect comparisons, the combination of pembrolizumab+ipilimumab showed a particularly high efficacy, and so deserves further investigation. While the effect of between\u2010trial differences in inclusion criteria plays an important role, our results do not support the proposal of relatlimab+nivolumab as a new standard of care.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cam4.5067","type":"journal-article","created":{"date-parts":[[2022,8,3]],"date-time":"2022-08-03T10:13:52Z","timestamp":1659521632000},"page":"2155-2165","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Immune checkpoint inhibitors as first line in advanced melanoma: Evaluating progression\u2010free survival based on reconstructed individual patient data"],"prefix":"10.1002","volume":"12","author":[{"given":"Andrea","family":"Ossato","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical and Pharmacological Sciences University of Padova  Padova Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3685-6789","authenticated-orcid":false,"given":"Vera","family":"Damuzzo","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical and Pharmacological Sciences University of Padova  Padova Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5106-7120","authenticated-orcid":false,"given":"Paolo","family":"Baldo","sequence":"additional","affiliation":[{"name":"Centro di Riferimento Oncologico di Aviano IRCCS  Aviano Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1374-1505","authenticated-orcid":false,"given":"Daniele","family":"Mengato","sequence":"additional","affiliation":[{"name":"Italian Society of Clinical Pharmacy and Therapeutics\u2010SIFaCT  Milan 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