Efficacy and Safety of Switching to Pasireotide LAR Alone or in Combination with Pegvisomant in Acromegaly Patients Controlled with Combination Treatment of First-Generation Somatostatin Analogues and Weekly Pegvisomant (PAPE study): A Prospective Open-Label 48 Week Study, Preliminary Results 24 Weeks
Presentation Number: SUN 427
Date of Presentation: April 2nd, 2017
Ammar Muhammad*1, Aart J. van der Lely2, Joseph A M J L Janssen3 and Sebastian J.C.M.M. Neggers2
1Erasmus University Medical Center Rotterdam, Rotterdam, Netherlands, 2Erasmus University Medical Center, Rotterdam, Netherlands, 3Erasmus Medical Center, Rotterdam, Netherlands
Introduction: 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 lead to a reduction in the required PEGV dose to normalize serum IGF1 levels, while the effect on glucose metabolism is not known. This is a prospective open-label study that assesses efficacy and safety of pasireotide LAR alone or in combination with PEGV.
Methods: We enrolled 60 acromegaly patients > 18 years with acromegaly who had normal IGF1 levels (≤ 1.2 x Upper Limit of Normal (ULN)) using combination treatment of high dose LA-SSAs and weekly PEGV for ≥ 6 months. We excluded acromegaly patients with an HbA1c ≥ 9.0% and patients who had undergone pituitary surgery or radiotherapy within 6 months prior to study entry.
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 x 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. Secondary endpoints included a safety assessment including the percentage of patients developing diabetes (defined as HbA1c ≥ 6.5% or fasting glucose ≥ 7 mmol/l or initiation of antidiabetic medication) at 24 weeks.
Results: At baseline, median IGF1 was 0.94 x ULN with a median PEGV dose of 80 mg/week, and 30.6% of patients had pre-existing diabetes with a median HbA1c of 5.9%. 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, after 3 injections of Pasireotide LAR, 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%. After 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, the most common adverse event was hyperglycemia/diabetes. At 12 weeks 33.3% of patients had diabetes with a median HbA1c 6.0%. At 24 weeks, the frequency of diabetes increased to 61.4%. At 24 weeks 29.8% of patients required no antidiabetic medication, while 38.6% of patients were respectively started on 1, 22.8% on 2, and 8.8% on 3 antidiabetic medications. Two patients withdrew prematurely due to hyperglycemia requiring insulin treatment. One patient had to be hospitalized for 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 hyperglycemia related-adverse events was 61.4% and is in line with previous studies.
Disclosure: AM: Coinvestigator, Novartis Pharmaceuticals. AJV: Consultant, Novartis Pharmaceuticals, Consultant, Pfizer, Inc., Consultant, Ipsen. SJCMMN: Consultant, Novartis Pharmaceuticals, Consultant, Pfizer, Inc., Consultant, Ipsen. Nothing to Disclose: JAMJLJ