{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T21:55:31Z","timestamp":1769810131920,"version":"3.49.0"},"reference-count":33,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T00:00:00Z","timestamp":1769731200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Italian Network for Tumor Bio-immunotherapy (NIBIT) Foundation Onlus"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background: Cutaneous squamous cell carcinoma (cSCC) represents the second most common form of non-melanoma skin malignancy, and, when not amenable to curative surgery or radiotherapy, it is a life-threatening disease. The anti-PD-1 monoclonal antibody cemiplimab has transformed the outcome of advanced or metastatic cSCC, with response rates approaching 50% and sustained benefit beyond three years in clinical trials. Cemiplimab is now the first-line standard of care treatment for advanced disease. Methods: This retrospective observational study included consecutive adult patients with locally advanced (lac) or metastatic (m) cSCC who received cemiplimab (350 mg every three weeks) at the Center for Immuno-Oncology, University Hospital of Siena, Italy, either through an Expanded Access Program or routine clinical practice. Clinical outcome and treatment related adverse events (TRAEs) are reported. Results: Between December 2019 and December 2023, 27 patients (24 male; median age 82 years [range 41\u201390]) diagnosed with lacSCC (n = 20 [74.0%]) or mcSCC (n = 7 [25.9%]) were treated with cemiplimab as first line therapy and were followed until June 2024. Head and neck were the primary tumor location for 88.8% of patients, followed by trunk (7.4%) and lower extremities (3.7%). All patients had comorbidities, including six patients (22.2%) with hematologic malignancies. With a median follow-up of 31 months (data cut-off June 2024), the ORR was 66.6% (complete response 22.2%) and the disease control rate (DCR) 77.7%. Median progression-free survival (mPFS) and overall survival (mOS) were not reached, while 2-year PFS and OS rates were 65.2% and 71%, respectively. Treatment was well-tolerated, with three (11.1%) patients experiencing grade \u22653 TRAEs, and three patients discontinuing treatment due to TRAEs. Conclusions: Our real-world experience confirms the high rate of durable objective responses, good tolerability and long treatment duration of cemiplimab in elderly and frail cSCC patients as well.<\/jats:p>","DOI":"10.3390\/cancers18030454","type":"journal-article","created":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T11:09:22Z","timestamp":1769771362000},"page":"454","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Real-World Experience of Cemiplimab in Patients with Advanced Cutaneous Squamous Cell Carcinoma"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-3332-7013","authenticated-orcid":false,"given":"Matteo","family":"Ravara","sequence":"first","affiliation":[{"name":"Department of Medicine, Surgery and Neurosciences, University of Siena, 53100 Siena, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tommaso","family":"Sani","sequence":"additional","affiliation":[{"name":"Department of Medicine, Surgery and Neurosciences, University of Siena, 53100 Siena, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9264-377X","authenticated-orcid":false,"given":"Vincenzo","family":"D\u2019Alonzo","sequence":"additional","affiliation":[{"name":"Department of Medicine, Surgery and Neurosciences, University of Siena, 53100 Siena, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6031-9916","authenticated-orcid":false,"given":"Monica","family":"Valente","sequence":"additional","affiliation":[{"name":"Center for Immuno-Oncology, University Hospital of Siena, 53100 Siena, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4009-0659","authenticated-orcid":false,"given":"Elisa","family":"Cinotti","sequence":"additional","affiliation":[{"name":"Dermatology Unit, Department of Medicine, Surgery and Neuroscience, University Hospital of Siena, 53100 Siena, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Clelia","family":"Miracco","sequence":"additional","affiliation":[{"name":"Department of Pathology, University Hospital of Siena, 53100 Siena, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maura","family":"Colucci","sequence":"additional","affiliation":[{"name":"Department of Medicine, Surgery and Neurosciences, University of Siena, 53100 Siena, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Valentina","family":"Croce","sequence":"additional","affiliation":[{"name":"Department of Medicine, Surgery and Neurosciences, University of Siena, 53100 Siena, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eleonora","family":"Carbonari","sequence":"additional","affiliation":[{"name":"Department of Medicine, Surgery and Neurosciences, University of Siena, 53100 Siena, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ramiz","family":"Rana","sequence":"additional","affiliation":[{"name":"Department of Medicine, Surgery and Neurosciences, University of Siena, 53100 Siena, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7674-0134","authenticated-orcid":false,"given":"Olindo","family":"Massarelli","sequence":"additional","affiliation":[{"name":"Maxillofacial Surgery Unit, Department of Medical Biotechnology, University Hospital of Siena, 53100 Siena, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giovanni","family":"Rubino","sequence":"additional","affiliation":[{"name":"Unit of Radiation Oncology, University Hospital of Siena, 53100 Siena, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Diana","family":"Giannarelli","sequence":"additional","affiliation":[{"name":"Department of Statistics, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8396-095X","authenticated-orcid":false,"given":"Roberto","family":"Cuomo","sequence":"additional","affiliation":[{"name":"Plastic Surgery Unit, Department of Medicine, Surgery and Neuroscience, University Hospital of Siena, 53100 Siena, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luca","family":"Grimaldi","sequence":"additional","affiliation":[{"name":"Plastic Surgery Unit, Department of Medicine, Surgery and Neuroscience, University Hospital of Siena, 53100 Siena, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pietro","family":"Rubegni","sequence":"additional","affiliation":[{"name":"Dermatology Unit, Department of Medicine, Surgery and Neuroscience, University Hospital of Siena, 53100 Siena, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michele","family":"Maio","sequence":"additional","affiliation":[{"name":"Department of Medicine, Surgery and Neurosciences, University of Siena, 53100 Siena, Italy"},{"name":"Center for Immuno-Oncology, University Hospital of Siena, 53100 Siena, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9315-2158","authenticated-orcid":false,"given":"Anna Maria","family":"Di Giacomo","sequence":"additional","affiliation":[{"name":"Department of Medicine, Surgery and Neurosciences, University of Siena, 53100 Siena, Italy"},{"name":"Center for Immuno-Oncology, University Hospital of Siena, 53100 Siena, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1016\/j.jaad.2017.08.059","article-title":"Cutaneous Squamous Cell Carcinoma","volume":"78","author":"Que","year":"2018","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1056\/NEJMoa1805131","article-title":"PD-1 Blockade with Cemiplimab in Advanced Cutaneous Squamous-Cell Carcinoma","volume":"379","author":"Migden","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1038\/s41568-023-00583-5","article-title":"Advances in Cutaneous Squamous Cell Carcinoma","volume":"23","author":"Winge","year":"2023","journal-title":"Nat. Rev. Cancer"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2379","DOI":"10.1158\/1078-0432.CCR-18-1122","article-title":"Keratinocyte Carcinomas: Current Concepts and Future Research Priorities","volume":"25","author":"Nagarajan","year":"2019","journal-title":"Clin. Cancer Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"3","DOI":"10.2340\/00015555-2181","article-title":"The Promise of Genomics and the Development of Targeted Therapies for Cutaneous Squamous Cell Carcinoma","volume":"96","author":"Harwood","year":"2016","journal-title":"Acta Derm. Venereol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"840","DOI":"10.1001\/jamadermatol.2018.1118","article-title":"Prevalence of Skin Cancer Examination Among Users of Indoor Tanning Beds","volume":"154","author":"Morris","year":"2018","journal-title":"JAMA Dermatol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1150","DOI":"10.1111\/bjd.15932","article-title":"Organ Transplantation and Cutaneous Squamous Cell Carcinoma: Progress, Pitfalls and Priorities in Immunosuppression-associated Keratinocyte Carcinoma","volume":"177","author":"Harwood","year":"2017","journal-title":"Br. J. Dermatol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1354","DOI":"10.1001\/jamadermatol.2015.4530","article-title":"Association Between \u03b2-Genus Human Papillomavirus and Cutaneous Squamous Cell Carcinoma in Immunocompetent Individuals\u2014A Meta-Analysis","volume":"152","author":"Chahoud","year":"2016","journal-title":"JAMA Dermatol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1038\/s41416-018-0105-y","article-title":"Heterogeneous Relationships of Squamous and Basal Cell Carcinomas of the Skin with Smoking: The UK Million Women Study and Meta-Analysis of Prospective Studies","volume":"119","author":"Pirie","year":"2018","journal-title":"Br. J. Cancer"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"560","DOI":"10.1016\/j.jaad.2017.10.007","article-title":"Guidelines of Care for the Management of Cutaneous Squamous Cell Carcinoma","volume":"78","author":"Kim","year":"2018","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"103005","DOI":"10.1016\/j.esmoop.2024.103005","article-title":"Guidelines for the Diagnosis and Treatment of Cutaneous Squamous Cell Carcinoma: A GRADE Approach for Evidence Evaluation and Recommendations by the Italian Association of Medical Oncology","volume":"9","author":"Queirolo","year":"2024","journal-title":"ESMO Open"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Baeza-Hern\u00e1ndez, G., and Ca\u00f1ueto, J. (2023). Intralesional Treatments for Invasive Cutaneous Squamous Cell Carcinoma. Cancers, 16.","DOI":"10.3390\/cancers16010158"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Alberti, A., and Bossi, P. (2022). Immunotherapy for Cutaneous Squamous Cell Carcinoma: Results and Perspectives. Front. Oncol., 11.","DOI":"10.3389\/fonc.2021.727027"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"e2021169S","DOI":"10.5826\/dpc.11S2a169S","article-title":"Immunotherapy and Systemic Treatment of Cutaneous Squamous Cell Carcinoma","volume":"11","author":"Morse","year":"2021","journal-title":"Dermatol. Pract. Concept."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1016\/j.ejca.2019.12.018","article-title":"Systemic Treatment of Patients with Advanced Cutaneous Squamous Cell Carcinoma: Response Rates and Outcomes of the Regimes Used","volume":"127","author":"Ogata","year":"2020","journal-title":"Eur. J. Cancer"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Javed, S.A., Najmi, A., Ahsan, W., and Zoghebi, K. (2024). Targeting PD-1\/PD-L-1 Immune Checkpoint Inhibition for Cancer Immunotherapy: Success and Challenges. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1383456"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"87","DOI":"10.3747\/co.27.5223","article-title":"A Review of Cancer Immunotherapy: From the Past, to the Present, to the Future","volume":"27","author":"Esfahani","year":"2020","journal-title":"Curr. Oncol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"6582","DOI":"10.1158\/1078-0432.CCR-14-1768","article-title":"Mutational Landscape of Aggressive Cutaneous Squamous Cell Carcinoma","volume":"20","author":"Pickering","year":"2014","journal-title":"Clin. Cancer Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1111\/cup.12728","article-title":"PD-L1 Expression in Cutaneous Squamous Cell Carcinoma Correlates with Risk of Metastasis","volume":"43","author":"Slater","year":"2016","journal-title":"J. Cutan. Pathol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1016\/S1470-2045(19)30728-4","article-title":"Cemiplimab in Locally Advanced Cutaneous Squamous Cell Carcinoma: Results from an Open-Label, Phase 2, Single-Arm Trial","volume":"21","author":"Migden","year":"2020","journal-title":"Lancet Oncol."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Kuzmanovszki, D., Kiss, N., T\u00f3th, B., T\u00f3th, V., Szakonyi, J., L\u0151rincz, K., H\u00e1rsing, J., Kuroli, E., Imr\u00e9di, E., and Kerner, T. (2023). Real-World Experience with Cemiplimab Treatment for Advanced Cutaneous Squamous Cell Carcinoma\u2014A Retrospective Single-Center Study. J. Clin. Med., 12.","DOI":"10.3390\/jcm12185966"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1007\/s40266-024-01095-z","article-title":"Real-World Experience of Immune-Checkpoint Inhibitors in Older Patients with Advanced Cutaneous Squamous Cell Carcinoma","volume":"41","author":"McLean","year":"2024","journal-title":"Drugs Aging"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Hober, C., Fredeau, L., Pham-Ledard, A., Boubaya, M., Herms, F., Celerier, P., Aubin, F., Beneton, N., Dinulescu, M., and Jannic, A. (2021). Cemiplimab for Locally Advanced and Metastatic Cutaneous Squamous-Cell Carcinomas: Real-Life Experience from the French CAREPI Study Group. Cancers, 13.","DOI":"10.1016\/j.annonc.2020.08.1210"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1016\/j.ejca.2021.08.018","article-title":"Real World Data of Cemiplimab in Locally Advanced and Metastatic Cutaneous Squamous Cell Carcinoma","volume":"157","author":"Baggi","year":"2021","journal-title":"Eur. J. Cancer"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Strippoli, S., Fanizzi, A., Quaresmini, D., Nardone, A., Armenio, A., Figliuolo, F., Filotico, R., Fucci, L., Mele, F., and Traversa, M. (2021). Cemiplimab in an Elderly Frail Population of Patients With Locally Advanced or Metastatic Cutaneous Squamous Cell Carcinoma: A Single-Center Real-Life Experience From Italy. Front. Oncol., 11.","DOI":"10.3389\/fonc.2021.686308"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"113251","DOI":"10.1016\/j.ejca.2023.113251","article-title":"European Consensus-Based Interdisciplinary Guideline for Invasive Cutaneous Squamous Cell Carcinoma. Part 1: Diagnostics and Prevention\u2013Update 2023","volume":"193","author":"Stratigos","year":"2023","journal-title":"Eur. J. Cancer"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"e002757","DOI":"10.1136\/jitc-2021-002757","article-title":"Integrated Analysis of a Phase 2 Study of Cemiplimab in Advanced Cutaneous Squamous Cell Carcinoma: Extended Follow-up of Outcomes and Quality of Life Analysis","volume":"9","author":"Rischin","year":"2021","journal-title":"J. Immunother. Cancer"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2916","DOI":"10.1200\/JCO.19.03054","article-title":"Pembrolizumab Monotherapy for Recurrent or Metastatic Cutaneous Squamous Cell Carcinoma: A Single-Arm Phase II Trial (KEYNOTE-629)","volume":"38","author":"Grob","year":"2020","journal-title":"J. Clin. Oncol."},{"key":"ref_29","first-page":"100875","article-title":"Cemiplimab in Locally Advanced or Metastatic Cutaneous Squamous Cell Carcinoma: Prospective Real-World Data from the DRUG Access Protocol","volume":"39","author":"Verkerk","year":"2024","journal-title":"Lancet Reg. Health-Eur."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"xi35","DOI":"10.1093\/annonc\/mdz451.006","article-title":"Impact of Prior Lines of Systemic Therapy (PST) on the Efficacy Of Cemiplimab, a Human Monoclonal Anti\u2013PD-1, in Patients (PTS) with Advanced Cutaneous Squamous Cell Carcinoma (CSCC)","volume":"30","author":"Rischin","year":"2019","journal-title":"Ann. Oncol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"100007","DOI":"10.1016\/j.ejcskn.2023.100007","article-title":"Real-World Data on Tolerability and Clinical Response of Cemiplimab in Patients with Advanced Cutaneous Squamous Cell Carcinoma: A Retrospective, Multicentre Cohort Study from the Netherlands","volume":"1","author":"Rohaan","year":"2023","journal-title":"EJC Skin Cancer"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Challapalli, A., Stewart, G., Shaw, H., Davies, P.J., Lopez-Baez, J.C., Ottley, E.C., and Kelly, S. (2024). Real-World Evidence Study on the Early Use of Cemiplimab in the UK: REACT-CEMI (Real World Evidence of Advanced CSCC Treatment with Cemiplimab). Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1408667"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"101640","DOI":"10.1016\/j.jgo.2023.101640","article-title":"Early Discontinuation of Cemiplimab in Patients with Advanced Cutaneous Squamous Cell Carcinoma","volume":"15","author":"Boutros","year":"2024","journal-title":"J. Geriatr. Oncol."}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/18\/3\/454\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T11:20:18Z","timestamp":1769772018000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/18\/3\/454"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,30]]},"references-count":33,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2026,2]]}},"alternative-id":["cancers18030454"],"URL":"https:\/\/doi.org\/10.3390\/cancers18030454","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,30]]}}}