EGFR/ErbB2-Targeting Lapatinib Therapy for Aggressive Prolactinomas

Odelia Cooper, Vivien S. Bonert, Jeremy Rudnick, Barry D. Pressman, Janet Lo, Roberto Salvatori, Kevin C.J. Yuen, Maria Fleseriu, Shlomo Melmed

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)E917-E925
JournalJournal of Clinical Endocrinology and Metabolism
Volume106
Issue number2
DOIs
StatePublished - Feb 1 2021
Externally publishedYes

Keywords

  • ErbB
  • HER2
  • epidermal growth factor receptor
  • lapatinib
  • prolactinoma
  • tyrosine kinase inhibitor

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical

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