{"doi":"10.1210/clinem/dgaa805","title":"EGFR/ErbB2-Targeting Lapatinib Therapy for Aggressive Prolactinomas","abstract":"CONTEXT: Approximately 10% to 20% of prolactinomas are resistant to dopamine agonist therapy. The ErbB signaling pathway may drive aggressive prolactinoma behavior. OBJECTIVE: We evaluated lapatinib, an ErbB1-epidermal growth factor receptor (EGFR)/ErbB2 or human EGFR2 (HER2) tyrosine kinase inhibitor (TKI), in aggressive prolactinomas. DESIGN: A prospective, phase 2a multicenter trial was conducted. SETTING: This study took place at a tertiary referral pituitary center. PATIENTS: Study participants included adults with aggressive prolactinomas showing continued tumor growth despite maximally tolerated dopamine agonist therapy. INTERVENTION: Intervention included oral lapatinib 1250 mg/day for 6 months. MAIN OUTCOME MEASURES: 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. RESULTS: 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. CONCLUSIONS: An oral TKI such as lapatinib may be an effective option for a difficult-to-treat patient with an aggressive prolactinoma.","journal":"The Journal of Clinical Endocrinology & Metabolism","year":2020,"id":59306,"datarank":1.9331351930806828,"base_score":4.23410650459726,"endowment":4.23410650459726,"self_citation_contribution":0.635115975689589,"citation_network_contribution":1.2980192173910938,"self_endowment_contribution":0.635115975689589,"citer_contribution":1.2980192173910938,"corpus_percentile":null,"corpus_rank":null,"citation_count":68,"citer_count":61,"citers_with_citation_signal":47,"citers_with_endowment":47,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9599,"is_data_producer":true,"deposit_databanks":{"ClinicalTrials.gov":["NCT00939523"]},"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":313121,"name":"Vivien Bonert","orcid":null,"position":1,"is_corresponding":false},{"id":311868,"name":"Jeremy Rudnick","orcid":"0000-0002-1442-4299","position":2,"is_corresponding":false},{"id":311869,"name":"Barry D. Pressman","orcid":"0000-0002-9080-7718","position":3,"is_corresponding":false},{"id":311870,"name":"Janet Lo","orcid":"0000-0002-5678-6140","position":4,"is_corresponding":false},{"id":311871,"name":"Roberto Salvatori","orcid":"0000-0001-6495-2244","position":5,"is_corresponding":false},{"id":311872,"name":"Kevin C.J. Yuen","orcid":"0000-0002-8169-2728","position":6,"is_corresponding":false},{"id":311873,"name":"Maria Fleseriu","orcid":"0000-0001-9284-6289","position":7,"is_corresponding":false},{"id":311874,"name":"Шломо Мелмед","orcid":"0000-0002-2355-3447","position":8,"is_corresponding":false},{"id":311867,"name":"Odelia Cooper","orcid":"0000-0001-5955-8242","position":0,"is_corresponding":true}],"reference_count":26,"raw_metadata":null,"created_at":"2026-07-18T21:07:59.189921Z","pmid":"33150390","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}