EGFR/ErbB2-Targeting Lapatinib Therapy for Aggressive Prolactinomas

• Published in: The journal of clinical endocrinology and metabolism 2021-02, Vol.106 (2), p.e917-e925
• Main Authors: Cooper, Odelia, Bonert, Vivien S, Rudnick, Jeremy, Pressman, Barry D, Lo, Janet, Salvatori, Roberto, Yuen, Kevin C J, Fleseriu, Maria, Melmed, Shlomo
• Format: Article
• Language: English
• Subjects: Adenoma; Aggressive behavior; Agonists; Bradycardia; Cabergoline; Care and treatment; Clinical s; Dopamine; Epidermal growth factor; Epidermal growth factor receptors; ErbB protein; ErbB-1 protein; ErbB-2 protein; Magnetic resonance imaging; Pituitary; Pituitary gland; Prolactin; Signal transduction; Solid tumors; Tumors; Tyrosine; Tyrosine kinase inhibitors
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/clinem/dgaa805

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.