Endocrine Abstracts (2013) 32 P847 | DOI: 10.1530/endoabs.32.P847

Switching patients with acromegaly from octreotide LAR to pasireotide LAR improves biochemical control: crossover extension to a randomized, double-blind, multicenter, Phase III study

Pamela Freda1, Maria Fleseriu2, Aart Jan van der Lely3, Annamaria Colao4, Michael Sheppard5, Feng Gu6, Chiung-Chyi Shen7,8, Monica Gadelha9, Andrew Farrall10, Karina Hermosillo Reséndiz11, Matthieu Ruffin12, YinMiao Chen11 & Marcello Bronstein13

1Columbia University College of Physicians & Surgeons, New York, New York, USA; 2Oregon Health & Science University, Portland, Oregon, USA; 3Erasmus University Medical Centre, Rotterdam, The Netherlands; 4Università Federico II di Napoli, Naples, Italy; 5University of Birmingham, Edgbaston, Birmingham, UK; 6Peking Union Medical College Hospital, Beijing, China; 7Tri-Service General Hospital and National Defense Medical Center, Taipei, Taiwan; 8Hungkuang University, Taichung, Taiwan; 9Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil; 10University of Edinburgh, Edinburgh, UK; 11Novartis Pharmaceuticals Corporation, Florham Park, New Jersey, USA; 12Novartis Pharma AG, Basel, Switzerland; 13University of São Paolo Medical School, São Paolo, Brazil.

Introduction: In a Phase III trial, pasireotide LAR was significantly superior (P=0.007) to octreotide LAR at providing biochemical control at 12 months in medically naïve acromegaly patients (post-pituitary surgery or de novo). Inadequately controlled patients (GH≥2.5 μg/l and/or IGF-1>ULN) at the end of core study were eligible for switching therapy (crossover extension). Reported here are efficacy results up to 12 months and safety results up to 13 months post-crossover.

Methods: Eligible patients were switched to either pasireotide LAR 40 mg/28 days (n=81) or octreotide LAR 20 mg/28 days (n=38). One dose escalation to pasireotide LAR 60 mg/28 days or octreotide LAR 30 mg/28 days was permitted, but not mandatory, post-crossover. Main outcome measures included GH<2.5 μg/l and normal IGF-1 12 months after switching medical therapy.

Results: A 31 pasireotide LAR and 13 octreotide LAR patients discontinued within 12 months after crossover. Response rates (95% CI) 12 months after crossover to pasireotide LAR (n=81) and octreotide LAR (n=38), respectively: GH<2.5 μg/l and normal IGF-1, 17.3% (9.8–27.3) and 0%; normal IGF-1, 27.2% (17.9–38.2) and 5.3% (0.6–17.7); GH<2.5 μg/l, 44.4% (33.4–55.9) and 23.7% (11.4–40.2); tumor volume decreased from extension baseline by a mean (SD) of 24.7% (25.2) and 17.9% (27.8). A significant (≥20%) tumor volume reduction from extension baseline was seen in 54.3% (25/46) of pasireotide LAR and 42.3% (11/26) of octreotide LAR patients. Safety profile of both agents was consistent with that seen in the core trial and with somatostatin analogues. Hyperglycemia-related AEs, while mostly mild or moderate, were more frequent with pasireotide LAR (64.2%) than octreotide LAR (21.1%). Fasting plasma glucose and HbA1c levels decreased to near normal levels within 3 months after switching from pasireotide LAR to octreotide LAR.

Conclusions: Pasireotide LAR holds promise as a treatment option for acromegaly patients inadequately controlled with octreotide LAR. Hyperglycemia associated with pasireotide LAR appeared to be reversible upon discontinuation of pasireotide.