{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T16:23:40Z","timestamp":1793118220448,"version":"4.5.0"},"reference-count":32,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2020,2,12]],"date-time":"2020-02-12T00:00:00Z","timestamp":1581465600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100000001","name":"Alberta Cancer Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000001","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Dr. Robert C. Westbury Melanoma Research Fund, Arnie Charbonneau Cancer Institute"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,5,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Objective response rates (ORR) appear to be higher in melanoma patients who develop immune-related adverse events (irAEs), but whether there is a similar association between irAEs and survival remains unknown.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>Patients with advanced melanoma treated with single-agent pembrolizumab or nivolumab in the province of Alberta from June 2014 to May 2017 were identified through the provincial pharmacy database. Chart review identified and categorized all irAEs that occurred while on anti\u2013programmed cell death protein 1 (PD-1) checkpoint inhibitors. The primary objective was to compare overall survival (OS) with patients who developed any irAEs versus those who did not. Secondary outcomes included progression-free survival (PFS) and ORR.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Among 186 patients, any-grade and grade \u22653 irAEs occurred in 88 (47%) and 27 (15%) patients, respectively; one patient died of pneumonitis. In a landmark analysis excluding patients who died within the first 12\u2009weeks, the median follow-up was 24 months, 20 months in patients without any irAEs and 26 months in patients with irAEs (p = .006). Median OS was 39 versus 23 months (hazard ratio [HR], 0.46; p = .001) for any irAE and no irAE, respectively, and median OS not reached versus 29 months for grade \u22653 irAEs and no grade \u22653 irAEs, respectively. In multivariate analysis, elevated lactate dehydrogenase correlated with reduced OS (HR, 2.34; p = .001), whereas each additional cycle of treatment received (HR, 0.94; p &amp;lt;\u2009.001) and development of grade \u22653 irAEs (HR, 0.29, p = .024) were significantly associated with longer OS.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Anti-PD-1\u2013associated grade \u22653 irAEs in patients with advanced melanoma is associated with better patient outcomes, including overall survival.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Implications for Practice<\/jats:title>\n                    <jats:p>Previous prospective randomized clinical trials demonstrate improved response rates in patients with melanoma who develop select adverse events. The current population-based real-world study in advanced melanoma reports an association with anti\u2013programmed cell death protein 1 (PD-1)\u2013induced grade \u22653 immune-related adverse events (irAEs) and better patient outcomes, including overall survival. These results suggest that irAEs may be a manifestation of a patient's ability to mount a systemic immune response from PD-1\u2013directed therapies, which may be associated with therapeutic benefit. The finding of irAEs coinciding with clinical benefit from these therapies supposes that these events are, by and large, unavoidable, and the critical management of irAEs remains essential for optimizing patient outcomes.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1634\/theoncologist.2019-0674","type":"journal-article","created":{"date-parts":[[2020,2,12]],"date-time":"2020-02-12T07:36:25Z","timestamp":1581492985000},"page":"438-446","source":"Crossref","is-referenced-by-count":74,"title":["Anti-PD1-Induced Immune-Related Adverse Events and Survival Outcomes in Advanced Melanoma"],"prefix":"10.1093","volume":"25","author":[{"given":"Aleksi","family":"Suo","sequence":"first","affiliation":[{"name":"Department\u2009of Oncology, University of Calgary, Calgary, Alberta, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yin","family":"Chan","sequence":"additional","affiliation":[{"name":"Department\u2009of Gastroenterology, University of Calgary, Calgary, 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