EGFR/ErbB2-Targeting Lapatinib Therapy for Aggressive Prolactinomas
Odelia Cooper1, Vivien S Bonert1, Jeremy Rudnick2
1Pituitary Center, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California.
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.
Insights
Lapatinib, an oral tyrosine kinase inhibitor, showed potential for aggressive prolactinomas resistant to standard therapy. While not meeting primary endpoints, it offered stable disease in some patients and was generally well-tolerated.
Area of Science:
- Endocrinology
- Oncology
- Pharmacology
Background:
- Approximately 10-20% of prolactinomas exhibit resistance to dopamine agonist therapy.
- The ErbB signaling pathway is implicated in the aggressive behavior of prolactinomas.
Purpose of the Study:
- To evaluate the efficacy and safety of lapatinib, an ErbB1-EGFR/ErbB2 tyrosine kinase inhibitor (TKI), in patients with aggressive prolactinomas.
- To assess tumor response, prolactin (PRL) reduction, and correlation with EGFR/HER2 expression.
Main Methods:
- A prospective, phase 2a, multicenter trial involving adults with aggressive prolactinomas resistant to dopamine agonists.
- Participants received oral lapatinib 1250 mg/day for 6 months.
- Tumor response assessed by Response Evaluation Criteria in Solid Tumors (RECIST) criteria; secondary endpoints included PRL reduction and safety.
Main Results:
- Due to stringent criteria, only 4 patients were treated; none achieved the primary endpoint of a 40% tumor dimension reduction.
- Three patients demonstrated stable disease, with tumor diameter changes ranging from a 6% increase to a 16.8% decrease.
- Lapatinib was generally well-tolerated, with manageable side effects including transaminitis, rash, and bradycardia.
Conclusions:
- Lapatinib may represent a viable therapeutic option for patients with aggressive prolactinomas refractory to conventional treatments.
- Further investigation is warranted to establish the role of TKIs in managing difficult-to-treat prolactinomas.
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