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.

• Authors: Odelia Cooper, Vivien S Bonert, Jeremy Rudnick, Barry D Pressman, Janet Lo, Roberto Salvatori, Kevin C J Yuen, Maria Fleseriu, Shlomo Melmed
• Journal: The Journal of clinical endocrinology and metabolism (J Clin Endocrinol Metab) Vol. 106 Issue 2 Pg. e917-e925 (01 23 2021) ISSN: 1945-7197 [Electronic] United States
• PMID: 33150390 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Research Support, N.I.H., Extramural)
• Copyright: © The Author(s) 2020. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: [email protected].

Chemical References

• Antineoplastic Agents
• Lapatinib
• EGFR protein, human
• ERBB2 protein, human
• ErbB Receptors
• Receptor, ErbB-2

Topics

• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Antineoplastic Agents (therapeutic use)
• ErbB Receptors (antagonists & inhibitors)
• Female
• Follow-Up Studies
• Gene Expression Regulation, Neoplastic (drug effects)
• Humans
• Lapatinib (therapeutic use)
• Male
• Middle Aged
• Pituitary Neoplasms (drug therapy, pathology)
• Prognosis
• Prolactinoma (drug therapy, pathology)
• Prospective Studies
• Receptor, ErbB-2 (antagonists & inhibitors)
• Young Adult