{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,17]],"date-time":"2025-11-17T17:21:49Z","timestamp":1763400109861,"version":"build-2065373602"},"reference-count":16,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2022,9,22]],"date-time":"2022-09-22T00:00:00Z","timestamp":1663804800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Department of Medicine (DAME) of the University of Udine"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Current Oncology"],"abstract":"<jats:p>The advent of immune checkpoint inhibitors in combination with multitarget tyrosine kinase inhibitors has become a standard first-line treatment for metastatic renal cell cancer. Along with survival improvement, new toxicities have emerged. Such adverse events are still complex to be managed and some of them are rare and could be insidious or even fatal. Medical oncologists dispose of guidelines about the management of toxicities from immune checkpoint inhibitors but not for combinations. Therefore, it is still difficult to properly attribute and manage additive or overlapping adverse events. We report two clinical cases regarding rare treatment-related endocrine toxicities\u2014hypophysitis and thyroiditis\u2014with particular focus on their management. To this purpose, immune checkpoint-related toxicities guidelines represent the starting point. However, their implementation with additional measures is needed, considering the increasing complexity of current clinical scenarios. The goal is to correctly recognize adverse events and address side effects, so as not to discontinue effective treatments. We, therefore, aim at discussing the points of proper management of toxicities and individuating potential areas of improvement.<\/jats:p>","DOI":"10.3390\/curroncol29100533","type":"journal-article","created":{"date-parts":[[2022,9,22]],"date-time":"2022-09-22T05:33:14Z","timestamp":1663824794000},"page":"6776-6786","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Rare and Insidious Toxicities from New Combination Therapies in Metastatic Renal Cell Cancer: Lessons Learned from Real-Practice"],"prefix":"10.3390","volume":"29","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6992-301X","authenticated-orcid":false,"given":"Arianna","family":"Dri","sequence":"first","affiliation":[{"name":"Department of Medicine (DAME), University of Udine, 33100 Udine, Italy"},{"name":"Department of Medical Oncology, Azienda Sanitaria Universitaria Friuli Centrale (ASUFC), 33100 Udine, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Silvio Ken","family":"Garattini","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Azienda Sanitaria Universitaria Friuli Centrale (ASUFC), 33100 Udine, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marika","family":"Cinausero","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Azienda Sanitaria Universitaria Friuli Centrale (ASUFC), 33100 Udine, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marianna","family":"Macerelli","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Azienda Sanitaria Universitaria Friuli Centrale (ASUFC), 33100 Udine, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martina","family":"Fanelli","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Azienda Sanitaria Universitaria Friuli Centrale (ASUFC), 33100 Udine, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0573-4938","authenticated-orcid":false,"given":"Fabio","family":"Puglisi","sequence":"additional","affiliation":[{"name":"Department of Medicine (DAME), University of Udine, 33100 Udine, Italy"},{"name":"Department of Medical Oncology, Centro di Riferimento Oncologico (CRO), IRCSS, 33081 Aviano, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1254-4705","authenticated-orcid":false,"given":"Gianpiero","family":"Fasola","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Azienda Sanitaria Universitaria Friuli Centrale (ASUFC), 33100 Udine, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paola","family":"Ermacora","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Azienda Sanitaria Universitaria Friuli Centrale (ASUFC), 33100 Udine, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,9,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1563","DOI":"10.1016\/S1470-2045(20)30436-8","article-title":"Pembrolizumab plus axitinib versus sunitinib monotherapy as first-line treatment of advanced renal cell carcinoma (KEYNOTE-426): Extended follow-up from a randomised, open-label, phase 3 trial","volume":"21","author":"Powles","year":"2020","journal-title":"Lancet Oncol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1030","DOI":"10.1016\/j.annonc.2020.04.010","article-title":"Updated efficacy results from the JAVELIN Renal 101 trial: First-line avelumab plus axitinib versus sunitinib in patients with advanced renal cell carcinoma","volume":"31","author":"Choueiri","year":"2020","journal-title":"Ann. Oncol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1056\/NEJMoa2026982","article-title":"Nivolumab plus Cabozantinib versus Sunitinib for Advanced Renal-Cell Carcinoma","volume":"384","author":"Choueiri","year":"2021","journal-title":"N. Engl. J. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1289","DOI":"10.1056\/NEJMoa2035716","article-title":"Lenvatinib plus Pembrolizumab or Everolimus for Advanced Renal Cell Carcinoma","volume":"384","author":"Motzer","year":"2021","journal-title":"N. Engl. J. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1016\/j.eururo.2018.07.019","article-title":"Re: Nivolumab plus Ipilimumab Versus Sunitinib in Advanced Renal-cell Carcinoma","volume":"74","author":"Powles","year":"2018","journal-title":"Eur. Urol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"iv119","DOI":"10.1093\/annonc\/mdx225","article-title":"Management of toxicities from immunotherapy: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up","volume":"28","author":"Haanen","year":"2017","journal-title":"Ann. Oncol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1714","DOI":"10.1200\/JCO.2017.77.6385","article-title":"Management of immune-related adverse events in patients treated with immune checkpoint inhibitor therapy: American Society of Clinical Oncology Clinical Practice Guideline","volume":"36","author":"Brahmer","year":"2018","journal-title":"J. Clin. Oncol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1038\/s41571-019-0218-0","article-title":"Adverse effects of immune-checkpoint inhibitors: Epidemiology, management and surveillance","volume":"16","author":"Martins","year":"2019","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"722","DOI":"10.1056\/NEJMoa1303989","article-title":"Pazopanib versus Sunitinib in Metastatic Renal-Cell Carcinoma","volume":"369","author":"Motzer","year":"2013","journal-title":"N. Engl. J. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1016\/j.euo.2021.03.001","article-title":"First-line Immunotherapy-based Combinations for Metastatic Renal Cell Carcinoma: A Systematic Review and Network Meta-analysis","volume":"4","author":"Quhal","year":"2021","journal-title":"Eur. Urol. Oncol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"102377","DOI":"10.1016\/j.ctrv.2022.102377","article-title":"New first-line immunotherapy-based combinations for metastatic renal cell carcinoma: A systematic review and network meta-analysis","volume":"106","author":"Lombardi","year":"2022","journal-title":"Cancer Treat. Rev."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1097\/JU.0000000000002252","article-title":"Clinical Outcomes and Adverse Events after First-Line Treatment in Metastatic Renal Cell Carcinoma: A Systematic Review and Network Meta-Analysis","volume":"207","author":"Nocera","year":"2022","journal-title":"J. Urol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"898","DOI":"10.1038\/s41416-020-0949-9","article-title":"Axitinib plus immune checkpoint inhibitor: Evidence- and expert-based consensus recommendation for treatment optimisation and management of related adverse events","volume":"123","author":"Voss","year":"2020","journal-title":"Br. J. Cancer"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1210\/er.2018-00006","article-title":"Endocrine Toxicity of Cancer Immunotherapy Targeting Immune Checkpoints","volume":"40","author":"Chang","year":"2018","journal-title":"Endocr. Rev."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"5083","DOI":"10.1200\/JCO.2020.38.15_suppl.5083","article-title":"Patient preferences and expectations of systemic therapy in renal cell carcinoma","volume":"38","author":"Battle","year":"2020","journal-title":"J. Clin. Oncol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1827","DOI":"10.1080\/03007995.2016.1211521","article-title":"The effect of information on preferences for treatments of metastatic renal cell carcinoma","volume":"32","author":"Mansfield","year":"2016","journal-title":"Curr. Med. Res. Opin."}],"container-title":["Current Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1718-7729\/29\/10\/533\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:37:08Z","timestamp":1760143028000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1718-7729\/29\/10\/533"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,9,22]]},"references-count":16,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2022,10]]}},"alternative-id":["curroncol29100533"],"URL":"https:\/\/doi.org\/10.3390\/curroncol29100533","relation":{},"ISSN":["1718-7729"],"issn-type":[{"type":"electronic","value":"1718-7729"}],"subject":[],"published":{"date-parts":[[2022,9,22]]}}}