{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T16:32:49Z","timestamp":1793118769806,"version":"4.5.0"},"reference-count":32,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T00:00:00Z","timestamp":1784764800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Anti-PD-1 immune checkpoint inhibitors have substantially changed melanoma management in both the adjuvant and advanced settings. This study aimed to estimate the percentage of stage III and IV melanoma patients exposed to different therapies and describe treatment patterns among anti-PD-1-treated patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We performed a retrospective chart review across 22 centers in Australia, France, Germany, South Korea, the United Kingdom, and the United States. Two patient populations were analyzed: (1) an aggregate cohort with stage III\/IV melanoma (2018-2021), and (2) patients who received anti-PD-1 therapy in adjuvant or advanced settings from January 2018\u201312 months before data collection. Treatment patterns were evaluated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In the aggregate cohort (N\u00a0=\u00a016,260), observation\/watchful waiting predominated in stage III patients (56.8%) in the adjuvant setting, whereas systemic therapy was most common for stage IV disease in the advanced setting. In the anti-PD-1 cohort (N\u00a0=\u00a0738), anti-PD-1 monotherapy predominated in the adjuvant setting (97.5%), while both anti-PD-1 monotherapy (63.1%) and anti-PD-1 plus anti-CTLA-4 (36.9%) were commonly used in the advanced setting. Across successive lines of therapy, anti-PD-1-based regimens remained frequently used despite substantial attrition between treatment lines. Disease progression was the leading cause of treatment discontinuation in advanced disease.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>This real-world study highlights the central role of anti-PD-1 therapy across disease stages. Anti-PD-1 retreatment and reuse of anti-PD-1-based regimens were frequently observed across treatment lines, highlighting the limited availability of established post-anti-PD-1 treatment options. Novel strategies are urgently needed for patients progressing after anti-PD-1 therapy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1813387","type":"journal-article","created":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T05:37:21Z","timestamp":1784785041000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Real-world treatment patterns in stage III and IV melanoma patients: insights from a global multi-center chart review study"],"prefix":"10.3389","volume":"17","author":[{"given":"Miso","family":"Kim","sequence":"first","affiliation":[{"name":"Seoul National University Hospital","place":["Seoul, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth M.","family":"Gaughan","sequence":"additional","affiliation":[{"name":"University of Virginia Cancer Center","place":["Charlottesville, VA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agueda","family":"Azpeitia","sequence":"additional","affiliation":[{"name":"OXON Epidemiology","place":["Madrid, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aparna","family":"Rao","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Peter MacCallum Cancer Centre","place":["Melbourne, VIC, Australia"]},{"name":"Melanoma Research Victoria","place":["Melbourne, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria L.","family":"Wei","sequence":"additional","affiliation":[{"name":"University of California, San Francisco, San Francisco","place":["CA, United States"]},{"name":"San Francisco VA Health Care System","place":["San Francisco, CA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"So","sequence":"additional","affiliation":[{"name":"University of California, San Francisco, San Francisco","place":["CA, United States"]},{"name":"San Francisco VA Health Care System","place":["San Francisco, CA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaochen","family":"Zhong","sequence":"additional","affiliation":[{"name":"University of California, San Francisco, San Francisco","place":["CA, United States"]},{"name":"San Francisco VA Health Care System","place":["San Francisco, CA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carola","family":"Berking","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Deutsches Zentrum Immuntherapie, Universit\u00e4tsklinikum Erlangen, CCC Erlangen-EMN, Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg","place":["Erlangen, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruixuan","family":"Jiang","sequence":"additional","affiliation":[{"name":"Merck Sharp & Dohme LLC (MSD), a subsidiary of Merck & Co., Inc.","place":["Rahway, NJ, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"St\u00e9phane","family":"Dalle","sequence":"additional","affiliation":[{"name":"Centre Hospitalier Lyon-Sud","place":["Pierre-Benite Cedex, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Robert","sequence":"additional","affiliation":[{"name":"Institut Gustave Roussy","place":["Villejuif, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salma","family":"Alam","sequence":"additional","affiliation":[{"name":"Mount Vernon Cancer Centre","place":["Northwood, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tessa","family":"Davies","sequence":"additional","affiliation":[{"name":"Velindre University NHS Trust","place":["Cardiff, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dirk","family":"Debus","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Nuremberg Hospital, Paracelsus Medical University","place":["Nuremberg, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcin","family":"Dzienis","sequence":"additional","affiliation":[{"name":"Gold Coast University Hospital","place":["Southport, QLD, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Danson","sequence":"additional","affiliation":[{"name":"Weston Park Cancer Centre, University of Sheffield and Sheffield Teaching Hospitals NHS Foundation Trust","place":["Sheffield, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ricky","family":"Frazer","sequence":"additional","affiliation":[{"name":"Velindre University NHS Trust","place":["Cardiff, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoffer","family":"Gebhardt","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Venereology, University Medical Center Hamburg-Eppendorf","place":["Hamburg, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Glenn","family":"Geidel","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Venereology, University Medical Center Hamburg-Eppendorf","place":["Hamburg, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica C.","family":"Hassel","sequence":"additional","affiliation":[{"name":"Heidelberg University, Medical Faculty Heidelberg, Department of Dermatology and National Center for Tumor Diseases (NCT), NCT Heidelberg, a partnership between DKFZ and University Hospital Heidelberg","place":["Heidelberg, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inga","family":"Hansen","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Venereology, University Medical Center Hamburg-Eppendorf","place":["Hamburg, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus V.","family":"Heppt","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Deutsches Zentrum Immuntherapie, Universit\u00e4tsklinikum Erlangen, CCC Erlangen-EMN, Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg","place":["Erlangen, Germany"]},{"name":"Dermpath M\u00fcnchen, Laboratory for Dermatopathology, Oral Pathology and Molecular Pathology","place":["Munich, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lina","family":"Hildebrandt","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Venereology, University Medical Center Hamburg-Eppendorf","place":["Hamburg, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Isaacs","sequence":"additional","affiliation":[{"name":"Cleveland Clinic","place":["Cleveland, OH, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koung Jin","family":"Suh","sequence":"additional","affiliation":[{"name":"Seoul National University Bundang Hospital, Seoul National University College of Medicine","place":["Seongnam, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bhumsuk","family":"Keam","sequence":"additional","affiliation":[{"name":"Seoul National University Hospital","place":["Seoul, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu Jung","family":"Kim","sequence":"additional","affiliation":[{"name":"Seoul National University Bundang Hospital, Seoul National University College of Medicine","place":["Seongnam, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thierry","family":"Lesimple","sequence":"additional","affiliation":[{"name":"Centre Eug\u00e9ne Marquis","place":["Rennes, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phillipe","family":"Saiag","sequence":"additional","affiliation":[{"name":"Department of General and Oncologic Dermatology, Ambroise Par\u00e9 hospital, APHP, & EA 4340 \u201cBiomarkers in cancerology and hemato-oncology\u201d, UVSQ, Universit\u00e9 Paris-Saclay","place":["Boulogne-Billancourt, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryan","family":"Weight","sequence":"additional","affiliation":[{"name":"The Melanoma and Skin Cancer Institute","place":["Englewood, CO, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alicia","family":"Delibes","sequence":"additional","affiliation":[{"name":"OXON Epidemiology","place":["Madrid, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosemarie","family":"Barnett","sequence":"additional","affiliation":[{"name":"OXON Epidemiology","place":["Madrid, Spain"]},{"name":"University of Bath","place":["Bath, United Kingdom"]},{"name":"Royal National Hospital for Rheumatic Diseases","place":["Bath, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clemens","family":"Krepler","sequence":"additional","affiliation":[{"name":"Merck Sharp & Dohme LLC (MSD), a subsidiary of Merck & Co., Inc.","place":["Rahway, NJ, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kavita","family":"Gandhi","sequence":"additional","affiliation":[{"name":"OXON Epidemiology","place":["Madrid, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nawab","family":"Qizilbash","sequence":"additional","affiliation":[{"name":"OXON Epidemiology","place":["Madrid, Spain"]},{"name":"The London School of Hygiene & Tropical Medicine","place":["London, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irene","family":"Shui","sequence":"additional","affiliation":[{"name":"Merck Sharp & Dohme LLC (MSD), a subsidiary of Merck & Co., Inc.","place":["Rahway, NJ, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiang-Lin","family":"Tan","sequence":"additional","affiliation":[{"name":"Merck Sharp & Dohme LLC (MSD), a subsidiary of Merck & Co., Inc.","place":["Rahway, NJ, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryan J.","family":"Sullivan","sequence":"additional","affiliation":[{"name":"Mass General Brigham Cancer Institute","place":["Boston, MA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,23]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.2217\/mmt.14.25","article-title":"Ipilimumab for the treatment of melanoma","volume":"2","author":"Jain","year":"2015","journal-title":"Melanoma Manag"},{"key":"B2","article-title":"Opdivo (nivolumab): second PD-1 inhibitor receives FDA approval for unresectable or metastatic melanoma","volume":"8","author":"Raedler","year":"2015","journal-title":"Am Health Drug Benefits"},{"key":"B3","unstructured":"FDA Approves pembrolizumab for advanced melanoma\n          \n          2014"},{"key":"B4","unstructured":"Opdivo\n          \n          2015"},{"key":"B5","unstructured":"New treatment option recommended for patients with advanced melanoma\n          \n          2015"},{"key":"B6","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1056\/NEJMoa2407417","article-title":"Final, 10-year outcomes with nivolumab plus ipilimumab in advanced melanoma","volume":"392","author":"Wolchok","year":"2025","journal-title":"N Engl J Med"},{"key":"B7","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1056\/NEJMoa2109970","article-title":"Relatlimab and nivolumab versus nivolumab in untreated advanced melanoma","volume":"386","author":"Tawbi","year":"2022","journal-title":"N Engl J Med"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2025.115547","article-title":"Nivolumab plus relatlimab in advanced melanoma: RELATIVITY-047 4-year update","volume":"225","author":"Lipson","year":"2025","journal-title":"Eur J Cancer"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1709030","article-title":"Adjuvant nivolumab versus ipilimumab in resected stage III or IV melanoma","volume":"377","author":"Weber","year":"2017","journal-title":"N Engl J Med"},{"key":"B10","unstructured":"Keytruda: EPAR \u2013 product information\n          \n          2018"},{"key":"B11","volume-title":"FDA approves pembrolizumab for adjuvant treatment of melanoma","year":"2019"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1056\/EVIDoa2200214","article-title":"Five-year analysis of adjuvant pembrolizumab or placebo in stage III melanoma","volume":"1","author":"Eggermont","year":"2022","journal-title":"NEJM Evid"},{"key":"B13","doi-asserted-by":"publisher","first-page":"3558","DOI":"10.3390\/cancers16213558","article-title":"Adjuvant use of pembrolizumab for stage III melanoma in a real-world setting in Europe","volume":"16","author":"Weichenthal","year":"2024","journal-title":"Cancers (Basel)"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2012.05.010","article-title":"Treatment patterns and outcomes among patients diagnosed with unresectable stage III or IV melanoma in Europe: a retrospective, longitudinal survey (MELODY study)","volume":"48","author":"Lebbe","year":"2012","journal-title":"Eur J Cancer"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1111\/jdv.14606","article-title":"Real-world treatment patterns and clinical outcomes in advanced cutaneous melanoma patients in France","volume":"32","author":"Sassolas","year":"2018","journal-title":"J Eur Acad Dermatol Venereol"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.2217\/cer-2019-0003","article-title":"Treatment patterns and outcomes for patients with unresectable stage III and metastatic melanoma in the USA","volume":"8","author":"Tarhini","year":"2019","journal-title":"J Comp Eff Res"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.2217\/fon-2018-0620","article-title":"Treatment patterns and outcomes for patients with advanced melanoma in US oncology clinical practices","volume":"15","author":"Whitman","year":"2019","journal-title":"Future Oncol"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2025.03.021","article-title":"Efficacy of adjuvant therapy in patients with stage IIIA cutaneous melanoma","volume":"36","author":"Grover","year":"2025","journal-title":"Ann Oncol"},{"key":"B19","unstructured":"NCCN guidelines - melanoma\n          \n          2025"},{"key":"B20","doi-asserted-by":"publisher","first-page":"389","DOI":"10.1186\/s12885-024-12178-w","article-title":"Assessing the use of anti-PD1 monotherapy as adjuvant therapy and determinants of treatment choice in stage III cutaneous melanoma in the US","volume":"24","author":"Whitman","year":"2024","journal-title":"BMC Cancer"},{"key":"B21","doi-asserted-by":"publisher","first-page":"1065","DOI":"10.1186\/s12889-019-7384-y","article-title":"Global comparison of cancer outcomes: standardization and correlation with healthcare expenditures","volume":"19","author":"Choi","year":"2019","journal-title":"BMC Public Health"},{"key":"B22","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1200\/CCI.18.00017","article-title":"Treatment options in oncology","volume":"2","author":"Panje","year":"2018","journal-title":"JCO Clin Cancer Inform"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2133.2011.10772.x","article-title":"Melanoma of the hand and foot: epidemiological, prognostic and genetic features. A systematic review","volume":"166","author":"Durbec","year":"2012","journal-title":"Br J Dermatol"},{"key":"B24","doi-asserted-by":"publisher","first-page":"160","DOI":"10.1007\/s12032-018-1218-0","article-title":"Duration of adjuvant immunotherapy-biologic, clinical and economic considerations","volume":"35","author":"Stav","year":"2018","journal-title":"Med Oncol"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2021.08.044","article-title":"Adjuvant treatment for melanoma in clinical practice - Trial versus reality","volume":"158","author":"de Meza","year":"2021","journal-title":"Eur J Cancer"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1111\/jdv.20650","article-title":"Early termination does not negatively impact the outcome of adjuvant immunotherapy in melanoma","volume":"39","author":"Tomsitz","year":"2025","journal-title":"J Eur Acad Dermatol Venereol"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.33800","article-title":"Discontinuation of anti-PD-1 monotherapy in advanced melanoma-outcomes of daily clinical practice","volume":"150","author":"van Zeijl","year":"2022","journal-title":"Int J Cancer"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdz110","article-title":"Discontinuation of anti-PD-1 antibody therapy in the absence of disease progression or treatment limiting toxicity: clinical outcomes in advanced melanoma","volume":"30","author":"Jansen","year":"2019","journal-title":"Ann Oncol"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1080\/0284186X.2020.1716388","article-title":"Limited-duration anti-PD-1 therapy for patients with metastatic melanoma","volume":"59","author":"Makela","year":"2020","journal-title":"Acta Oncol"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1097\/CMR.0000000000000858","article-title":"Survivals following discontinuation of PD-1 inhibitor treatment in advanced melanoma patients","volume":"33","author":"Kartolo","year":"2023","journal-title":"Melanoma Res"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.2217\/fon-2021-0340","article-title":"Treatment patterns and outcomes following disease progression on anti-PD-1 therapies for advanced melanoma","volume":"18","author":"Nordstrom","year":"2022","journal-title":"Future Oncol"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1002\/cam4.2625","article-title":"Real-world survival of patients with advanced BRAF V600 mutated melanoma treated with front-line BRAF\/MEK inhibitors, anti-PD-1 antibodies, or nivolumab\/ipilimumab","volume":"8","author":"Moser","year":"2019","journal-title":"Cancer Med"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1813387\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T05:37:22Z","timestamp":1784785042000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1813387\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,23]]},"references-count":32,"alternative-id":["10.3389\/fimmu.2026.1813387"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2026.1813387","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,23]]},"article-number":"1813387"}}