The Journal of clinical endocrinology and metabolism · 2021
EGFR/ErbB2-Targeting Lapatinib Therapy for Aggressive Prolactinomas.
Клиническое исследование II фазыСтатьяМногоцентровое исследованиеПоддержка NIH: внешняя программаНазвание и аннотация: Перевод в очереди
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Cooper Odelia, Bonert Vivien S, Rudnick Jeremy, Pressman Barry D, Lo Janet, Salvatori Roberto, Yuen Kevin C J, Fleseriu Maria, Melmed Shlomo
Аннотация
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.
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.