Efficacy and safety of switching to pasireotide in patients with acromegaly controlled with pegvisomant and first-generation somatostatin analogues (PAPE Study)

Aim: To assess the efficacy and safety of pasireotide long-Acting release (PAS-LAR) alone or in combination with pegvisomant by switching patients with acromegaly who were well controlled with long-Acting somatostatin analogues (LA-SSAs) and pegvisomant to PAS-LAR with or without pegvisomant. Methods: Sixty-one patients with acromegaly were enrolled in a prospective open-label study. We included patients with an insulin-like growth factor I (IGF-I) #1.2 3 upper limit of normal (ULN) during treatment with LA-SSAs and pegvisomant. At baseline, the pegvisomant dose was reduced by 50% up to 12 weeks. When IGF-I remained#1.23ULN after 12 weeks, patients were switched to PAS-LAR 60 mg monotherapy. When IGF-I was .1.2 3 ULN, patients were switched to PAS-LAR 60 mg, and they continued with the 50% reduced pegvisomant dose. Results: At baseline, mean IGF-I was 0.97 3 ULN, and the median pegvisomant dose was 80 mg/wk. At 12 weeks, mean IGF-I increased to 1.59 3 ULN, and IGF-I levels #1.2 ULN were observed in 24.6% of participants. At 24 weeks, IGF-I levels were reduced into the reference range in 73.8% of patients. Between baseline and 24 weeks, the pegvisomant dose was reduced by 66.1%. PAS-LAR was well tolerated, but hyperglycemia was the most frequent adverse event. The frequency of diabetes increased from 32.8% at baseline to 68.9% at 24 weeks. Conclusions: Switching to PAS-LAR, either as monotherapy or combination with pegvisomant, can control IGF-I levels in most patients. PAS-LAR demonstrated a pegvisomant-sparing effect of 66% compared with the combination with LA-SSAs. Hyperglycemia was the most important safety issue.