{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T12:23:01Z","timestamp":1791894181867,"version":"4.3.4"},"reference-count":26,"publisher":"The Endocrine Society","issue":"2","license":[{"start":{"date-parts":[[2020,11,5]],"date-time":"2020-11-05T00:00:00Z","timestamp":1604534400000},"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\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R21DK105405"],"award-info":[{"award-number":["R21DK105405"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006108","name":"National Center for Advancing Translational Sciences","doi-asserted-by":"publisher","award":["UL1TR000124"],"award-info":[{"award-number":["UL1TR000124"]}],"id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006108","name":"National Center for Advancing Translational Sciences","doi-asserted-by":"publisher","award":["UL1TR001881"],"award-info":[{"award-number":["UL1TR001881"]}],"id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,1,23]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Context<\/jats:title>\n                  <jats:p>Approximately 10% to 20% of prolactinomas are resistant to dopamine agonist therapy. The ErbB signaling pathway may drive aggressive prolactinoma behavior.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>We evaluated lapatinib, an ErbB1-epidermal growth factor receptor (EGFR)\/ErbB2 or human EGFR2 (HER2) tyrosine kinase inhibitor (TKI), in aggressive prolactinomas.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Design<\/jats:title>\n                  <jats:p>A prospective, phase 2a multicenter trial was conducted.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Setting<\/jats:title>\n                  <jats:p>This study took place at a tertiary referral pituitary center.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Patients<\/jats:title>\n                  <jats:p>Study participants included adults with aggressive prolactinomas showing continued tumor growth despite maximally tolerated dopamine agonist therapy.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Intervention<\/jats:title>\n                  <jats:p>Intervention included oral lapatinib 1250 mg\/day for 6 months.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Main Outcome Measures<\/jats:title>\n                  <jats:p>The primary end point was 40% reduction in any tumor dimension assessed by magnetic resonance imaging at study end; tumor response was assessed by Response Evaluation Criteria in Solid Tumors criteria. Secondary end points included prolactin (PRL) reduction, correlation of response with EGFR\/HER2 expression, and safety.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Owing to rigorous inclusion criteria, of 24 planned participants, only 7 consented and 4 were treated. None achieved the primary end point but 3 showed stable disease, including 2 with a 6% increase and 1 with a 16.8% decrease in tumor diameter. PRL response was not always concordant with tumor response, as 2 showed 28% and 59% increases in PRL. The fourth participant had a PRL-secreting carcinoma and withdrew after 3 months of lapatinib because of imaging and PRL progression. EGFR\/HER2 expression did not correlate with treatment response. Lapatinib was well tolerated overall, with reversible grade 1 transaminitis in 2 patients, grade 2 rash in 2 patients, and grade 1 asymptomatic bradycardia in 2 patients.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>An oral TKI such as lapatinib may be an effective option for a difficult-to-treat patient with an aggressive prolactinoma.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1210\/clinem\/dgaa805","type":"journal-article","created":{"date-parts":[[2020,11,5]],"date-time":"2020-11-05T04:23:24Z","timestamp":1604550204000},"page":"e917-e925","source":"Crossref","is-referenced-by-count":67,"title":["EGFR\/ErbB2-Targeting Lapatinib Therapy for Aggressive Prolactinomas"],"prefix":"10.1210","volume":"106","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5955-8242","authenticated-orcid":false,"given":"Odelia","family":"Cooper","sequence":"first","affiliation":[{"name":"Pituitary Center, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vivien S","family":"Bonert","sequence":"additional","affiliation":[{"name":"Pituitary Center, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeremy","family":"Rudnick","sequence":"additional","affiliation":[{"name":"Departments of Medicine, Neurology, and Neurosurgery, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barry D","family":"Pressman","sequence":"additional","affiliation":[{"name":"Department of Imaging, Cedars-Sinai Medical Center, Los Angeles, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janet","family":"Lo","sequence":"additional","affiliation":[{"name":"Neuroendocrine Unit, Massachusetts General Hospital, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6495-2244","authenticated-orcid":false,"given":"Roberto","family":"Salvatori","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Diabetes, and Metabolism and Pituitary Center, Johns Hopkins Hospital, Baltimore, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin C J","family":"Yuen","sequence":"additional","affiliation":[{"name":"Department of Neuroendocrinology and Neurosurgery, Barrow Pituitary Center, Barrow Neurological Institute, University of Arizona College of Medicine and Creighton School of Medicine, Phoenix, Arizona"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Fleseriu","sequence":"additional","affiliation":[{"name":"Pituitary Center, Departments of Medicine (Endocrinology) and Neurological Surgery, Oregon Health & Science University, Portland, Oregon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2355-3447","authenticated-orcid":false,"given":"Shlomo","family":"Melmed","sequence":"additional","affiliation":[{"name":"Pituitary Center, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","published-online":{"date-parts":[[2020,11,5]]},"reference":[{"issue":"11","key":"2021122205330407000_CIT0001","doi-asserted-by":"crossref","first-page":"5256","DOI":"10.1210\/jcem.86.11.8054","article-title":"Resistance to cabergoline as compared with bromocriptine in hyperprolactinemia: prevalence, clinical definition, and 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