Improvement of Biochemical Control in Patients with Acromegaly Switched from Octreotide LAR to Pasireotide LAR: Crossover Extension to a Double-Blind, Multicenter, Randomized, Phase III Study

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: SUN 88-129-Acromegaly & Prolactinoma
Sunday, June 16, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board SUN-95
Pamela U Freda*1, Maria Fleseriu2, Aart Jan van der Lely3, Annamaria Colao4, Michael C Sheppard5, Feng Gu6, Chiung-Chyi Shen7, Monica Gadelha8, Andrew J Farrall9, Karina Hermosillo Reséndiz10, Matthieu Ruffin11, YinMiao Chen10 and Marcello D Bronstein12
1Columbia University College of Physicians & Surgeons, New York, NY, 2Northwest Pituitary Center, Oregon Health & Science University, Portland, OR, 3Erasmus MC, Rotterdam, Netherlands, 4Università Federico II di Napoli, Naples, Italy, 5University of Birmingham, Birmingham, United Kingdom, 6Peking Union Medical College Hospital, Beijing, China, 7Tri-Service General Hospital and National Defense Medical Center, Taipei, Taiwan, 8Federal University of Rio de Janeiro, Rio de Janeiro, Brazil, 9University of Edinburgh, Edinburgh, United Kingdom, 10Novartis Pharmaceuticals Corporation, Florham Park, NJ, 11Novartis Pharma AG, Basel, Switzerland, 12University of São Paulo Medical School, São Paulo, Brazil
Introduction: In a Phase III trial, pasireotide LAR was found to be 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≥2.5µg/L and/or IGF-1>ULN) at the end of the 12-month core study were eligible for switching therapy (crossover extension). Reported here are efficacy results up to 12 months after crossover and safety results up to 13 months after crossover.

Methods: Eligible patients were switched to either pasireotide LAR 40mg/28d (n=81) or octreotide LAR 20mg/28d (n=38). One dose escalation to pasireotide LAR 60mg/28d or octreotide LAR 30mg/28d was permitted, but not mandatory, after crossover. Dose decrease to pasireotide LAR 20 mg/28d or octreotide LAR 10 mg/28d was permitted at any time in the event of tolerability issues. Main outcome measures included GH<2.5μg/L and normal IGF-1 12 months after switching medical therapy.

Results: 31 (38%) pasireotide LAR and 13 (34%) 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, were as follows: GH<2.5μg/L and normal IGF-1, 17.3% (9.8–27.3) and 0%; GH<2.5µg/L, 44.4% (33.4–55.9) and 23.7% (11.4–40.2); normal IGF-1, 27.2% (17.9–38.2) and 5.3% (0.6–17.7). Median percentage change in tumor volume from extension baseline was –22.1% (n=46) with pasireotide LAR and –11.8% (n=26) with octreotide LAR. 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. The safety profile of both the agents following crossover was consistent with that seen in the core trial: 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.

Disclosure: PUF: Medical Advisory Board Member, Novartis Pharmaceuticals, Investigator, Novartis Pharmaceuticals. MF: Consultant, Ipsen, Investigator, Novartis Pharmaceuticals, Investigator, Ipsen, Consultant, Novartis Pharmaceuticals. AC: Committee Member, Novartis Pharmaceuticals. MCS: Consultant, Novartis Pharmaceuticals, Speaker, Novartis Pharmaceuticals. MG: Speaker, Novartis Pharmaceuticals, Speaker, Ipsen, Speaker, Pfizer, Inc., Investigator, Pfizer, Inc., Investigator, Novartis Pharmaceuticals, Medical Advisory Board Member, Novartis Pharmaceuticals. AJF: Consultant, Novartis Pharmaceuticals, Investigator, Novartis Pharmaceuticals. KHR: Employee, Novartis Pharmaceuticals. MR: Employee, Novartis Pharmaceuticals, Employee, Novartis Pharmaceuticals. YC: Employee, Novartis Pharmaceuticals. MDB: Speaker, Ipsen, Speaker, Novartis Pharmaceuticals, , Ipsen, Committee Member, Novartis Pharmaceuticals, Committee Member, Chiasma, Investigator, Novartis Pharmaceuticals. Nothing to Disclose: AJV, FG, CCS

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