Pegvisomant as Monotherapy or Combination Therapy in Somatostatin Refractory Acromegaly

Abstract

Abstract Background: Pegvisomant, a growth hormone antagonist, has been widely used as monotherapy or combination therapy with somatostatin (SST) analogs and/or dopamine agonists in acromegaly poorly controlled by SST analogs. Limited information is available to compare pegvisomant monotherapy, combination with SST analogs or dopamine agonists, and combination of all three agents. Method: In this retrospective cohort study, we identified 23 patients with SST analog refractory acromegaly who received pegvisomant as monotherapy or in combination with SST analogs and/or dopamine agonists through the Research Patient Data Registry. We divided the patients into four groups: Group 1. pegvisomant alone (n=8); Group 2. pegvisomant plus a SST analog (pasireotide, octreotide or lanreotide) (n=8); Group 3. pegvisomant plus cabergoline (n=5) Group 4. Pegvisomant plus SST analog and dopamine agonist (n=2). We analyzed the changes in IGF-1, HbA1C, ALT and AST, blood pressure, and radiographic tumor size before and 6 months after treatment. Results: In 6 months, the mean IGF-1 level (ng/ml) changed from baseline 482 to 290 and decreased by 40% (P = 0.050) in group 1, changed from baseline 623 to 291 and decreased by 53% (P= 0.003) in group 2, changed from baseline 579 to 367 and decreased by 36% (p = 0.100) in group 3, and decreased 47% from 609 to 326 (P= 0.100) in group 4. The mean systolic blood pressure (mmHg) before and 6 months after treatment changed from 139 to 128 (p = 0.001) in group 1, changed from 130 to 126 (p = 0.553) in group 2, changed from 134 to 126 (p = 0.373) in group 3, and changed from 125 to 127 (p= 0.700) in group 4. Diastolic blood pressure (mmHg) changed from 82 to 76 (P = 0.110) in group 1, changed from 79 to 76 (p = 0.325) in group 2, changed from 80 to 74 (p=0.002) in group 3, and changed from 80 to 75 (p=0.126) in group 4. There were no significant changes in ALT and AST and A1C before and 6 months after treatment in all groups. In terms of radiographic tumor size change before and 6 months after the treatment, there was no change in tumor size in 5 of 5 patients in group 1. In group 2, the tumor size in 4 of 7 remained unchanged but 3 of 7 patients had increased tumor sizes. In group 3, there was no change in tumor size in 3 of 3 patients. In group 4, there was no change in tumor size in 2 of 2 patients. Conclusion: Our results suggest that in somatostain analog refractory acromegaly, combination pegvisomant and a SST analog significantly decreased IGF-1 level although decrease in IGF-1 in pegvisomant monotherapy almost reach statistical significance (P = 0.050). Although there was a trend in decrease of blood pressure in all groups, the decrease reached significant significance in systolic blood pressure in group 1 and diastolic blood pressure in group 3. Finally, except group 2, the tumor size remained unchanged.