Somatotroph tumor progression during pegvisomant therapy: a clinical and molecular study.

Context: There is concern that pegvisomant could be associated with a higher risk of tumor growth. The rate and possible determinants of this tumor growth are unknown.

Objective: The objective of the study was to investigate the clinical, immunohistological, and molecular factors conditioning tumor growth in patients taking pegvisomant.

Design And Setting: This was a cross-sectional study performed from 2004 to 2010 in four university hospitals in Spain.

Patients: Seventy-five acromegalic patients with active disease resistant to somatostatin analogs treated with pegvisomant were followed up for a mean of 29 ± 20 months.

Main Outcome Measures: Magnetic resonance images before initiation of pegvisomant, at 6 months, and then yearly were examined in all patients. Immunohistological and molecular studies were performed in tumors that grew.

Results: A significant increase in tumor size was observed in five patients (6.7%). Absence of previous irradiation (P = 0.014) and shorter duration of prepegvisomant somatostatin analog therapy (P < 0.001) were associated with an increased risk of tumor growth. A stepwise multivariate linear regression analysis (R(2) = 0.334, P < 0.001) identified the duration of somatostatin analog therapy prior to pegvisomant (beta = -4.509, P = 0.014) as the only significant predictor of tumor growth. In those tumors that grew, GH expression and insulin receptor expression were higher (P = 0.033 in both cases) than in the control group.

Conclusions: No previous radiotherapy, shorter duration of prepegvisomant somatostatin analog therapy, and higher tumor expression of GH and insulin receptor could be risk factors for tumor growth during pegvisomant therapy.