Endocrine Abstracts

Introduction: Combination therapy using pegvisomant and cabergoline with first-generation long-acting somatostatin analogs (1GSSA) is a common procedure in acromegalic patients that are not fully controlled by surgery and 1GSSA. Pasireotide-LAR is a new multireceptor-targeted somatostatin receptor ligand that has superior efficacy over octreotide LAR to control GH and IGF1 levels. Little data is available about the efficacy and safety of pasireotide monotherapy in patients treated with a combination therapy.

Materiel and methods: Fourteen acromegalic patients (10 women, aged: 47±11 y) treated with octreotide LAR (30 mg/Mo, N=8) or lanreotide SR (120 mg/Mo, N=6), and cabergoline (N=4, weekly dose=3.5 mg) or pegvisomant (N=10, weekly dose 40–200 mg) were prospectively enrolled in an open study and switched to pasireotide-LAR monotherapy (half with 40 mg and half with 60 mg/Mo). Seven patients already had diabetes mellitus, two patients had glucose intolerance. Clinical, biological and radiological evaluations were performed before (baseline), 3 months after the switch and at 6 Mo or later.

Results: IGF1 level at 3 Mo and baseline were similar (median=1.1 vs 1.1 ULN). Median GH was 1.54 ng/ml (min=0.14-max=8.9). As compared to baseline, six patients vs five had IGF1 below 1ULN. A significant increase in fasting blood glucose and HbA1c was observed at 3 Mo vs baseline: 1.15 g/l (0.82–1.6) vs 1.02 (0.9–1.78) (P=0.05) and 6.4% (5.4–8.4) vs 5.7% (5.3–7.2) (P=0.002) respectively. A new anti-diabetic treatment was initiated in six patients (including five with diabetes at baseline). During the follow-up, six patients stopped Pasireotide-LAR for lack of control of IGF-1 (N=2), intolerance despite control (dizziness N=1 and hyperglycemia N=1), and lack of control associated with hyperglycemia (N=2). Eight patients were treated with Pasireotide-LAR for a median duration of 8 months (2–17) with a controlled IGF1 (0.5–1.1 ULN) and acceptable glucose tolerance (median HbA1c 6.1% (5.4–7.4)). Three of these 8 patients required antidiabetic treatment intensification (increase in insulin dosage in 1) or initiation (oral antidiabetic treatments in two). Five patients had normal glucose tolerance without pharmacological treatment.

Conclusion: In this small series, Pasireotide-LAR is an efficient alternative with acceptable tolerance in a subset of acromegalic patients treated with a combination therapy involving 1GSSA.