Pasireotide LAR maintains inhibition of GH and IGF-1 in patients with acromegaly for up to 25 months: results from the blinded extension phase of a randomized, double-blind, multicenter, Phase III study.

Michael Sheppard,Liudmila Rozhinskaya,Matthieu Ruffin,Pamela Freda,Laura De Marinis,Karina Hermosillo Reséndiz,Annamaria Colao,Omar Serri,Marcello D Bronstein,Yinmiao Chen,Luciana Naves

doi:10.1007/s11102-014-0585-6

Abstract

PurposeA large, randomized, double-blind, Phase III core study demonstrated that pasireotide LAR was significantly superior to octreotide LAR at providing GH <2.5 μg/L and normalized IGF-1 after 12 months’ treatment in patients with acromegaly. We report the efficacy and safety of pasireotide LAR and octreotide LAR after up to 26 months’ treatment.MethodsPatients with GH <2.5 μg/L and IGF-1 ≤1× ULN at month 12, or patients considered to be experiencing clinical benefit, were eligible to continue receiving their randomized therapy in the extension. Efficacy and safety in the pasireotide LAR and octreotide LAR groups were evaluated for up to 26 months.ResultsOverall, 120 patients who completed the core study continued receiving pasireotide LAR (n = 74) or octreotide LAR (n = 46) in the extension. At month 25, biochemical control (GH <2.5 μg/L and normal IGF-1) was achieved by 48.6 % (36/74) and 45.7 % (21/46) of patients in the pasireotide LAR and octreotide LAR arms [60.8 % (45/74) and 52.2 % (24/46) when including patients with IGF-1 < LLN], respectively. In total, 74.7 % of pasireotide LAR and 71.6 % of octreotide LAR patients had tumor volume decrease ≥20 % from baseline to month 26. Most AEs were mild or moderate. Hyperglycemia-related AEs were seen in 62.9 and 25.0 % of pasireotide LAR and octreotide LAR patients, respectively. No new safety signals were observed in the extension compared with the core study.ConclusionsGH and IGF-1 suppression is maintained for up to 25 months during pasireotide LAR treatment. The safety profile of pasireotide LAR is typical of a somatostatin analogue, except for the frequency and degree of hyperglycemia.Electronic supplementary materialThe online version of this article (doi:10.1007/s11102-014-0585-6) contains supplementary material, which is available to authorized users.

Highlights

Is characterized by chronic hypersecretion of growth hormone (GH), which primarily originates from a GH-secreting pituitary adenoma and induces the synthesis of insulin-like growth factor 1 (IGF-1)
141/176 (80.1 %) and 156/182 (85.7 %) patients in the pasireotide long-acting release (LAR) and octreotide LAR arms, respectively, completed the 12-month core study. Of those patients who completed the core study, 74 pasireotide LAR patients and 46 octreotide LAR patients continued on their randomized therapy in the extension phase (Table 1; Fig. 2)
If GH and IGF-1 assessments were taken [35 days after the pasireotide LAR or octreotide LAR injection, these values were considered to be missing at the corresponding visit

Summary

Introduction

Is characterized by chronic hypersecretion of growth hormone (GH), which primarily originates from a GH-secreting pituitary adenoma and induces the synthesis of insulin-like growth factor 1 (IGF-1). As decreasing GH to \2.5 lg/L and IGF-1 to normal levels significantly reduces mortality [1,2,3,4], the main treatment goal for acromegaly is to control GH and IGF-1 levels. Long-acting somatostatin analogues are the cornerstone of medical therapy for acromegaly and are indicated in patients with failed surgery or as first-line treatment when surgery is contraindicated or declined [6, 7]. In selected patients with active acromegaly, long-term somatostatin analogue therapy has been demonstrated to effectively control GH and IGF-1 levels, induce tumor volume reduction and improve hypertension and cardiac performance [9, 10, 12]. Many patients with acromegaly do not achieve biochemical control with the currently available somatostatin analogues [14]

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Results

Conclusion