Odelia Cooper1, Vivien S Bonert1, Jeremy Rudnick2, Barry D Pressman3, Janet Lo4, Roberto Salvatori5, Kevin C J Yuen6, Maria Fleseriu7, Shlomo Melmed1. 1. Pituitary Center, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California. 2. Departments of Medicine, Neurology, and Neurosurgery, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California. 3. Department of Imaging, Cedars-Sinai Medical Center, Los Angeles, California. 4. Neuroendocrine Unit, Massachusetts General Hospital, Boston, Massachusetts. 5. Division of Endocrinology, Diabetes, and Metabolism and Pituitary Center, Johns Hopkins Hospital, Baltimore, Maryland. 6. Department of Neuroendocrinology and Neurosurgery, Barrow Pituitary Center, Barrow Neurological Institute, University of Arizona College of Medicine and Creighton School of Medicine, Phoenix, Arizona. 7. Pituitary Center, Departments of Medicine (Endocrinology) and Neurological Surgery, Oregon Health & Science University, Portland, Oregon.
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.
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.
Authors: A Di Sarno; M L Landi; P Cappabianca; F Di Salle; F W Rossi; R Pivonello; C Di Somma; A Faggiano; G Lombardi; A Colao Journal: J Clin Endocrinol Metab Date: 2001-11 Impact factor: 5.958
Authors: Ulf Elbelt; Sven M Schlaffer; Michael Buchfelder; Ulrich J Knappe; Greisa Vila; Alexander Micko; Timo Deutschbein; Nicole Unger; Alexander Lammert; Tengü Topuzoglu-Müller; Jörg Bojunga; Michael Droste; Sarah Johanssen; Herbert Kolenda; Katrin Ritzel; Rolf Buslei; Christian J Strasburger; Stephan Petersenn; Jürgen Honegger Journal: J Clin Endocrinol Metab Date: 2020-03-01 Impact factor: 5.958