{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T21:44:02Z","timestamp":1792705442541,"version":"4.5.0"},"reference-count":24,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"31","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["JCO"],"published-print":{"date-parts":[[2024,11]]},"abstract":"<jats:sec>\n                    <jats:title>PURPOSE<\/jats:title>\n                    <jats:p>Retrospective studies suggest that immunosuppressive treatment of immune-related adverse events (irAEs) impairs survival in patients with melanoma who received immune checkpoint inhibitors. Here, we study this association across tumor types using data from six international phase II\/III registrational trials.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>A post hoc analysis was performed on individual patient data from the anti\u2013programmed cell death-1 (anti\u2013PD-1) + anti\u2013cytotoxic T lymphocyte\u2013associated protein-4 (anti\u2013CTLA-4) treatment arms of six clinical trials (CheckMate-067, -142, -214, -648, -743, and -9LA). Among patients who received systemic immunosuppression for treatment-related adverse events (trAEs), associations of peak and cumulative corticosteroid dose, and use of second-line immunosuppression with overall survival (OS) and progression-free survival (PFS) were assessed using multilevel Cox regression with adjustment for age and sex.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      Of the 1,959 patients who received anti\u2013PD-1 + anti\u2013CTLA-4 therapy, 834 patients who were treated with immunosuppression for trAEs were included. Eight hundred and thirty-two patients (100%) received corticosteroids and 81 patients (10%) received second-line immunosuppressants. High corticosteroid peak dose was associated with worse PFS: adjusted hazard ratio (HR\n                      <jats:sub>adj<\/jats:sub>\n                      ), 1.15 (95% CI, 1.02 to 1.29) for 1 versus 0.5 mg\/kg prednisolone and HR\n                      <jats:sub>adj<\/jats:sub>\n                      , 1.43 (95% CI, 1.05 to 1.96) for 2 versus 0.5 mg\/kg. Similar effects were observed for OS: HR\n                      <jats:sub>adj<\/jats:sub>\n                      , 1.21 (95% CI, 1.06 to 1.39) and HR\n                      <jats:sub>adj<\/jats:sub>\n                      , 1.66 (95% CI, 1.17 to 2.37) for 1 and 2 versus 0.5 mg\/kg, respectively. Cumulative corticosteroid dose was not associated with survival. HR\n                      <jats:sub>adj<\/jats:sub>\n                      of use of second-line immunosuppression was 1.23 (95% CI, 0.90 to 1.68) for PFS and 1.25 (95% CI, 0.88 to 1.77) for OS.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>Higher corticosteroid peak dose for trAEs is associated with worse survival across tumor types, while cumulative dose is not. Too few patients received second-line immunosuppressants to confirm or reject an association with survival. These data argue for a reconsideration of irAE management approaches, starting with lower corticosteroid dose whenever feasible.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1200\/jco.24.00191","type":"journal-article","created":{"date-parts":[[2024,8,7]],"date-time":"2024-08-07T16:01:07Z","timestamp":1723046467000},"page":"3713-3724","update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":125,"title":["Corticosteroids for Immune-Related Adverse Events and Checkpoint Inhibitor Efficacy: Analysis of Six Clinical Trials"],"prefix":"10.1200","volume":"42","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1966-1063","authenticated-orcid":false,"given":"Rik J.","family":"Verheijden","sequence":"first","affiliation":[{"name":"Department of Medical Oncology, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands"},{"name":"Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Centre Utrecht, Utrecht University, Utrecht, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jolien S.","family":"de Groot","sequence":"additional","affiliation":[{"name":"Medicines Evaluation Board, Utrecht, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5924-3977","authenticated-orcid":false,"given":"Babs O.","family":"Fabriek","sequence":"additional","affiliation":[{"name":"Medicines Evaluation Board, Utrecht, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miki N.","family":"Hew","sequence":"additional","affiliation":[{"name":"Medicines Evaluation Board, Utrecht, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0643-3790","authenticated-orcid":false,"given":"Anne M.","family":"May","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Centre Utrecht, Utrecht University, Utrecht, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3604-5430","authenticated-orcid":false,"given":"Karijn P.M.","family":"Suijkerbuijk","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"233","reference":[{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2022.10.001"},{"key":"e_1_3_5_3_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.21.01440"},{"key":"e_1_3_5_4_2","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2021-002435"},{"key":"e_1_3_5_5_2","doi-asserted-by":"publisher","DOI":"10.2217\/imt-2020-0179"},{"key":"e_1_3_5_6_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2019.5570"},{"key":"e_1_3_5_7_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-21-1283"},{"key":"e_1_3_5_8_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-19-3322"},{"key":"e_1_3_5_9_2","article-title":"Corticosteroids and other immunosuppressants for immune-related adverse events and checkpoint inhibitor effectiveness in melanoma","author":"Verheijden RJ","unstructured":"Verheijden RJ, Burgers FH, Janssen JC, et al: Corticosteroids and other immunosuppressants for immune-related adverse events and checkpoint inhibitor effectiveness in melanoma. Eur J Cancer 10.1016\/j.ejca.2024.114172 [epub ahead of print on June 15, 2024]","journal-title":"Eur J Cancer"},{"key":"e_1_3_5_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2023.09.2291"},{"key":"e_1_3_5_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41698-023-00380-1"},{"key":"e_1_3_5_12_2","unstructured":"ECOG-ACRIN Cancer Research Group: ECOG performance status scale. ECOG-ACRIN Cancer Research Group. https:\/\/ecog-acrin.org\/resources\/ecog-performance-status\/"},{"key":"e_1_3_5_13_2","unstructured":"National Cancer Institute: Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. https:\/\/ctep.cancer.gov\/protocolDevelopment\/electronic_applications\/ctc.htm"},{"key":"e_1_3_5_14_2","volume-title":"Goodman & Gilman\u2019s: The Pharmacological Basis of Therapeutics","author":"Schimmer BP","year":"2017","unstructured":"Schimmer BP, Funder JW: Adrenocorticotropic hormone, adrenal steroids, and the adrenal cortex, in Brunton LL, Hilal-Dandan R, Knollmann BC (eds): Goodman & Gilman\u2019s: The Pharmacological Basis of Therapeutics (ed 13). New York, NY, McGraw-Hill Education, 2017. https:\/\/accessmedicine.mhmedical.com\/content.aspx?bookid=2189&sectionid=172482605","edition":"13"},{"key":"e_1_3_5_15_2","doi-asserted-by":"publisher","DOI":"10.1002\/jrsm.1384"},{"key":"e_1_3_5_16_2","doi-asserted-by":"publisher","DOI":"10.1002\/sim.1009"},{"key":"e_1_3_5_17_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1504030"},{"key":"e_1_3_5_18_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2017.76.9901"},{"key":"e_1_3_5_19_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1712126"},{"key":"e_1_3_5_20_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2111380"},{"key":"e_1_3_5_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(20)32714-8"},{"key":"e_1_3_5_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(20)30641-0"},{"key":"e_1_3_5_23_2","doi-asserted-by":"publisher","DOI":"10.1111\/apt.17201"},{"key":"e_1_3_5_24_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.d549"},{"key":"e_1_3_5_25_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.21.01015"}],"container-title":["Journal of Clinical Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ascopubs.org\/doi\/pdfdirect\/10.1200\/JCO.24.00191","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,10,29]],"date-time":"2024-10-29T17:59:45Z","timestamp":1730224785000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascopubs.org\/doi\/10.1200\/JCO.24.00191"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11]]},"references-count":24,"journal-issue":{"issue":"31","published-print":{"date-parts":[[2024,11]]}},"alternative-id":["10.1200\/JCO.24.00191"],"URL":"https:\/\/doi.org\/10.1200\/jco.24.00191","relation":{},"ISSN":["0732-183X","1527-7755"],"issn-type":[{"value":"0732-183X","type":"print"},{"value":"1527-7755","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,11]]},"assertion":[{"value":"2024-01-30","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-04-14","order":1,"name":"revised","label":"Revised","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-05-22","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-08-07","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}