Efficacy and safety of long-acting pasireotide in patients with somatostatin-resistant acromegaly: a multicenter study

Pasireotide, a multi-somatostatin receptor (SSTR)-ligand with high affinity for SSTR₅ was recently approved for acromegaly treatment.

A retrospective multicenter study investigating the efficacy and safety of long-acting (LAR) pasireotide treatment in 35 patients (20 males) with active acromegaly (28 macroadenomas).

Mean baseline insulin-like growth factor-1 (IGF-1) at diagnosis was 3.1 ± 1.3 × ULN. All but five patients have undergone pituitary surgery and six received sellar radiotherapy. All remained with active acromegaly despite first-generation somatostatin analogue (SSA) treatment. Immediately before pasireotide-LAR initiation, eighteen patients were under SSA monotherapy and one with pegvisomant. The remaining patients received combination therapy with SSA and pegvisomant, n = 9 (two received cabergoline also); SSA and cabergoline, n = 4; pegvisomant and cabergoline, n = 1. Two were untreated. Mean IGF-1 was 1.76 ± 0.9 ULN before pasireotide. Pasireotide-LAR starting dose was 40 mg/4 weeks in most patients. IGF-1 normalized in 19 patients, IGF-1 between 1-1.2 × ULN was reached in five, and in additional two patients IGF-1 was significantly suppressed. No effect was seen in nine patients. Pasireotide dose was reduced by 20 mg in six patients with excellent response, with preserved IGF-1 control in five. Severe headaches in six patients disappeared or improved with pasireotide. Side effects consisted of symptomatic cholelithiasis in one patient and deterioration of glucose control in 22 patients, requiring initiation or intensification of antidiabetic treatment in seventeen. One patient developed diabetic ketoacidosis.

In the real-life scenario ~54% of patients with acromegaly resistant to first-generation SSA, may normalize IGF-1 with pasireotide; however, 63% experienced glucose control deterioration.