{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T23:55:45Z","timestamp":1788306945146,"version":"build-2803163510"},"reference-count":19,"publisher":"The Endocrine Society","issue":"11","license":[{"start":{"date-parts":[[2025,3,20]],"date-time":"2025-03-20T00:00:00Z","timestamp":1742428800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R21 CA280469-01"],"award-info":[{"award-number":["R21 CA280469-01"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100021671","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["P30 CA008748"],"award-info":[{"award-number":["P30 CA008748"]}],"id":[{"id":"10.13039\/501100021671","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012231","name":"Society of Memorial Sloan Kettering","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100012231","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008021","name":"Bristol Myers Squibb","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008021","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,10,16]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Context<\/jats:title>\n                    <jats:p>Pituitary neuroendocrine tumors (PitNETs) that progress following surgery and radiotherapy are in need of additional treatment options. Responses to immune checkpoint inhibitors (ICIs) have been described; however, the feasibility of ICI therapy and biomarkers of response have not been formally assessed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To evaluate the activity of ICI as a treatment for PitNETs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We performed a single-center, prospective, phase 2 trial investigating the activity of ipilimumab and nivolumab in patients with PitNETs. The primary endpoint was objective response using the iRANO response criteria. We then explored genetic biomarkers of response to ICIs in 13 patients with PitNETs who were treated with ICIs, on or outside of the trial.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Ten patients with a PitNET were enrolled, including 5 corticotroph, 4 lactotroph, and 1 somatotroph tumor, of which 9\/10 (4 metastatic and 5 nonmetastatic) patients were evaluable for the primary endpoint. While no objective responses were observed, tumor shrinkage was seen in 2\/9 patients. In a biomarker discovery cohort, comprising 7 tumors treated on trial and 6 tumors treated off trial, temozolomide hypermutation, and mismatch repair deficiency (MMRd) were associated with immunological response. In 3 tumors sequenced pre- and post-ICI treatment, we identified evidence of immunoediting, characterized by loss of MMRd and\/or a decrease in tumor mutational burden.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study demonstrates the safety and feasibility of ICI treatment in aggressive PitNETs. We also identified MMRd and temozolomide hypermutation as potential biomarkers of response to ICI. Overall, our data suggest that ICIs might provide an additional treatment option for PitNET; this should be evaluated more broadly in future studies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1210\/clinem\/dgaf178","type":"journal-article","created":{"date-parts":[[2025,3,19]],"date-time":"2025-03-19T00:20:14Z","timestamp":1742343614000},"page":"3066-3073","source":"Crossref","is-referenced-by-count":15,"title":["Immune Checkpoint Inhibitor Therapy for Aggressive Pituitary Neuroendocrine Tumors"],"prefix":"10.1210","volume":"110","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0659-261X","authenticated-orcid":false,"given":"Andrew L","family":"Lin","sequence":"first","affiliation":[{"name":"Department of Neurosurgery, Memorial Sloan Kettering Cancer Center , New York, NY 10065 ,","place":["USA"]},{"name":"Department of Neurology, Memorial Sloan Kettering Cancer Center , New York, NY 10065 ,","place":["USA"]},{"name":"Multidisciplinary Pituitary and Skull Base Tumor Center, Memorial Sloan Kettering Cancer Center , New York, NY 10065 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vasilisa","family":"Rudneva","sequence":"additional","affiliation":[{"name":"Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center , New York, NY 10065 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam","family":"Newton","sequence":"additional","affiliation":[{"name":"Department of Neurology, Memorial Sloan Kettering Cancer Center , New York, NY 10065 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nazanin K","family":"Majd","sequence":"additional","affiliation":[{"name":"Department of Neuro-oncology, The University of Texas MD Anderson Cancer Center , Houston, TX 77030 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajiv","family":"Magge","sequence":"additional","affiliation":[{"name":"Department of Neurology, Weill Cornell Medical Center , New York, NY 10021 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soma","family":"Sengupta","sequence":"additional","affiliation":[{"name":"Department of Neurology and Neurosurgery, and the Lineberger Comprehensive Cancer Center, University of North Carolina , Chapel Hill, NC 27517 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernard","family":"Goichot","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Les H\u00f4pitaux Universitaires de Strasbourg F-67098 , Strasbourg ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Piotrowski","sequence":"additional","affiliation":[{"name":"Department of Neurology, Memorial Sloan Kettering Cancer Center , New York, NY 10065 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Igor","family":"Gavrilovic","sequence":"additional","affiliation":[{"name":"Department of Neurology, Memorial Sloan Kettering Cancer Center , New York, NY 10065 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5955-8242","authenticated-orcid":false,"given":"Odelia","family":"Cooper","sequence":"additional","affiliation":[{"name":"Pituitary Center, Cedars-Sinai Medical Center , Los Angeles, CA 90048 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc","family":"Rosenblum","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center , New York, NY 10065 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Kaley","sequence":"additional","affiliation":[{"name":"Department of Neurology, Memorial Sloan Kettering Cancer Center , New York, NY 10065 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4347-8149","authenticated-orcid":false,"given":"Ingo","family":"Mellinghoff","sequence":"additional","affiliation":[{"name":"Department of Neurology, Memorial Sloan Kettering Cancer Center , New York, NY 10065 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert J","family":"Young","sequence":"additional","affiliation":[{"name":"Department of Radiology, Memorial Sloan Kettering, Cancer Center , New York, NY 10065 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark T A","family":"Donoghue","sequence":"additional","affiliation":[{"name":"Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center , New York, NY 10065 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Viviane","family":"Tabar","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Memorial Sloan Kettering Cancer Center , New York, NY 10065 ,","place":["USA"]},{"name":"Multidisciplinary Pituitary and Skull Base Tumor Center, Memorial Sloan Kettering Cancer Center , New York, NY 10065 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3722-1889","authenticated-orcid":false,"given":"Eliza B","family":"Geer","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Memorial Sloan Kettering Cancer Center , New York, NY 10065 ,","place":["USA"]},{"name":"Multidisciplinary Pituitary and Skull Base Tumor Center, Memorial Sloan Kettering Cancer Center , New York, NY 10065 ,","place":["USA"]},{"name":"Department of Medicine, Memorial Sloan Kettering Cancer Center , New York, NY 10065 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","published-online":{"date-parts":[[2025,3,20]]},"reference":[{"issue":"1","key":"2025101519592333000_dgaf178-B1","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1007\/s00401-024-02736-8","article-title":"Genome-wide loss of heterozygosity predicts aggressive, treatment-refractory behavior in pituitary neuroendocrine tumors","volume":"147","author":"Lin","year":"2024","journal-title":"Acta Neuropathol"},{"issue":"1","key":"2025101519592333000_dgaf178-B2","doi-asserted-by":"crossref","first-page":"G1","DOI":"10.1530\/EJE-17-0796","article-title":"European Society of Endocrinology clinical practice guidelines for the management of aggressive pituitary tumours and carcinomas","volume":"178","author":"Raverot","year":"2018","journal-title":"Eur J Endocrinol"},{"issue":"4","key":"2025101519592333000_dgaf178-B3","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1530\/EJE-22-0440","article-title":"Aggressive pituitary tumours and carcinomas, characteristics and management of 171 patients","volume":"187","author":"Burman","year":"2022","journal-title":"Eur J Endocrinol"},{"issue":"3","key":"2025101519592333000_dgaf178-B4","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1530\/EJE-17-0933","article-title":"Treatment of aggressive pituitary tumours and carcinomas: results of a European Society of Endocrinology (ESE) survey 2016","volume":"178","author":"McCormack","year":"2018","journal-title":"Eur J Endocrinol"},{"issue":"10","key":"2025101519592333000_dgaf178-B5","doi-asserted-by":"crossref","first-page":"3925","DOI":"10.1210\/jc.2018-01347","article-title":"Marked response of a hypermutated ACTH-secreting pituitary carcinoma to ipilimumab and nivolumab","volume":"103","author":"Lin","year":"2018","journal-title":"J Clin Endocrinol Metab"},{"issue":"7463","key":"2025101519592333000_dgaf178-B6","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1038\/nature12477","article-title":"Signatures of mutational processes in human cancer","volume":"500","author":"Alexandrov","year":"2013","journal-title":"Nature"},{"issue":"4","key":"2025101519592333000_dgaf178-B7","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1111\/cen.14645","article-title":"Should pituitary carcinoma be treated using a NET-like approach? A case of complete remission of a metastatic malignant prolactinoma with multimodal therapy including immunotherapy","volume":"98","author":"Goichot","year":"2023","journal-title":"Clin Endocrinol (Oxf)"},{"issue":"2","key":"2025101519592333000_dgaf178-B8","doi-asserted-by":"crossref","first-page":"e51","DOI":"10.1227\/neu.0000000000002024","article-title":"Complete response of a patient with a mismatch repair deficient aggressive pituitary adenoma to immune checkpoint inhibitor therapy: a case report","volume":"91","author":"Shah","year":"2022","journal-title":"Neurosurgery"},{"issue":"5","key":"2025101519592333000_dgaf178-B9","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1530\/EJE-22-0647","article-title":"Real-life efficacy and predictors of response to immunotherapy in pituitary tumors: a cohort study","volume":"187","author":"Ilie","year":"2022","journal-title":"Eur J Endocrinol"},{"issue":"2","key":"2025101519592333000_dgaf178-B10","doi-asserted-by":"crossref","first-page":"e001532","DOI":"10.1136\/jitc-2020-001532","article-title":"Efficacy of pembrolizumab in patients with pituitary carcinoma: report of four cases from a phase II study","volume":"8","author":"Majd","year":"2020","journal-title":"J Immunother Cancer"},{"issue":"15","key":"2025101519592333000_dgaf178-B11","doi-asserted-by":"crossref","first-page":"e534","DOI":"10.1016\/S1470-2045(15)00088-1","article-title":"Immunotherapy response assessment in neuro-oncology: a report of the RANO working group","volume":"16","author":"Okada","year":"2015","journal-title":"Lancet Oncol"},{"issue":"10","key":"2025101519592333000_dgaf178-B12","doi-asserted-by":"crossref","first-page":"bvab133","DOI":"10.1210\/jendso\/bvab133","article-title":"Synergism of checkpoint inhibitors and peptide receptor radionuclide therapy in the treatment of pituitary carcinoma","volume":"5","author":"Lin","year":"2021","journal-title":"J Endocr Soc"},{"issue":"3","key":"2025101519592333000_dgaf178-B13","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1016\/j.jmoldx.2014.12.006","article-title":"Memorial sloan kettering-integrated mutation profiling of actionable cancer targets (MSK-IMPACT): a hybridization capture-based next-generation sequencing clinical assay for solid tumor molecular oncology","volume":"17","author":"Cheng","year":"2015","journal-title":"J Mol Diagn"},{"issue":"7766","key":"2025101519592333000_dgaf178-B14","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1038\/s41586-019-1382-1","article-title":"Tumour lineage shapes BRCA-mediated phenotypes","volume":"571","author":"Jonsson","year":"2019","journal-title":"Nature"},{"issue":"1","key":"2025101519592333000_dgaf178-B15","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1056\/NEJMoa1504030","article-title":"Combined nivolumab and ipilimumab or monotherapy in untreated melanoma","volume":"373","author":"Larkin","year":"2015","journal-title":"N Engl J Med"},{"issue":"12","key":"2025101519592333000_dgaf178-B16","doi-asserted-by":"crossref","first-page":"1402","DOI":"10.1038\/ng.3441","article-title":"Clock-like mutational processes in human somatic cells","volume":"47","author":"Alexandrov","year":"2015","journal-title":"Nat Genet"},{"issue":"2","key":"2025101519592333000_dgaf178-B17","doi-asserted-by":"crossref","first-page":"e917","DOI":"10.1210\/clinem\/dgaa805","article-title":"EGFR\/ErbB2-targeting lapatinib therapy for aggressive prolactinomas","volume":"106","author":"Cooper","year":"2021","journal-title":"J Clin Endocrinol Metab"},{"issue":"11","key":"2025101519592333000_dgaf178-B18","doi-asserted-by":"crossref","first-page":"3928","DOI":"10.1210\/jc.2017-01401","article-title":"Corticotroph pituitary carcinoma in a patient with lynch syndrome (LS) and pituitary tumors in a nationwide LS cohort","volume":"102","author":"Bengtsson","year":"2017","journal-title":"J Clin Endocrinol Metab"},{"issue":"7","key":"2025101519592333000_dgaf178-B19","doi-asserted-by":"crossref","first-page":"1585","DOI":"10.1210\/clinem\/dgad098","article-title":"Aggressive pituitary tumors and pituitary carcinomas: from pathology to treatment","volume":"108","author":"Burman","year":"2023","journal-title":"J Clin Endocrinol Metab"}],"container-title":["The Journal of Clinical Endocrinology &amp; Metabolism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jcem\/advance-article-pdf\/doi\/10.1210\/clinem\/dgaf178\/62480135\/dgaf178.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jcem\/article-pdf\/110\/11\/3066\/62480135\/dgaf178.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jcem\/article-pdf\/110\/11\/3066\/62480135\/dgaf178.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,15]],"date-time":"2025-10-15T23:59:31Z","timestamp":1760572771000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jcem\/article\/110\/11\/3066\/8087917"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,20]]},"references-count":19,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2025,3,20]]},"published-print":{"date-parts":[[2025,10,16]]}},"URL":"https:\/\/doi.org\/10.1210\/clinem\/dgaf178","relation":{},"ISSN":["0021-972X","1945-7197"],"issn-type":[{"value":"0021-972X","type":"print"},{"value":"1945-7197","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2025,11]]},"published":{"date-parts":[[2025,3,20]]}}}