Endocrine Abstracts

Background: Efficacy and safety of combination treatment of pasireotide LAR with pegvisomant (PEGV) has not been studied yet. Switching to Pasireotide LAR in patients previously controlled with long-acting somatostatin analogues (LA-SSAs) and PEGV could reduce the required PEGV dose to normalize serum IGF1 levels, while the effect on glucose metabolism is unknown.

Methods: We enrolled 60 acromegaly patients >18 years with acromegaly who had normal IGF1 levels (≤1.2×Upper Limit of Normal (ULN)) using combination treatment of high dose LA-SSAs and weekly PEGV for ≥6 months. After enrollment LA-SSA treatment was continued, and the PEGV dose was reduced by 50% for 12 weeks. If IGF1 levels remained normal after 12 weeks, patients were switched to pasireotide LAR 60 mg monotherapy, every 4 weeks. If IGF1 levels >1.2×ULN patients were switched to pasireotide LAR 60 mg and continued with the 50% reduced PEGV dose. The primary endpoint was the percentage of patients achieving normal IGF1 levels at 24 weeks. The key secondary endpoint was the frequency diabetes at 24 weeks.

Results: At baseline, median IGF1 was 0.94×ULN with a median PEGV dose of 80 mg/week, and 30.6% of patients had pre-existing diabetes. After the 50% dose reduction of PEGV, median IGF1 levels increased to 1.43 ULN, while IGF1 remained normal in 33% of patients. At 24 weeks, 73% of patients achieved normal IGF1 levels with a median IGF1 0.98×ULN. Cumulative PEGV dose reduction between baseline and 24 weeks was 66%. At 24 weeks, IGF1 levels were normal in 88% of patients on pasireotide LAR monotherapy, and 68% of patients on combination treatment. Pasireotide LAR was well tolerated. At 24 weeks, the most common adverse event was diabetes which occurred in 70.2% of patients. Two patients withdrew prematurely due to hyperglycemia requiring insulin treatment.

Conclusion: Pasireotide LAR alone or in combination with pegvisomant controls IGF1 in 73% of patients after 66% reduction in cumulative dose of weekly pegvisomant. The frequency of diabetes was 70.2% and is in line with previous studies.