FP27-4 Pasireotide LAR and Octreotide LAR Normalize Prolactin Levels in Patients with Acromegaly and Hyperprolactinemia: Results from a Randomized, Double-Blind, 12-Month, Phase III Study

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: FP27-Pituitary: Acromegaly and Prolactinoma
Sunday, June 16, 2013: 10:45 AM-11:15 AM
Presentation Start Time: 11:00 AM
Room 135 (Moscone Center)

Poster Board SUN-89
Annamaria Colao*1, Marcello D Bronstein2, Feng Gu3, Karina Hermosillo Reséndiz4, Matthieu Ruffin5, YinMiao Chen4 and Pamela U Freda6
1Università Federico II di Napoli, Naples, Italy, 2University of São Paulo Medical School, São Paulo, Brazil, 3Peking Union Medical College Hospital, Beijing, China, 4Novartis Pharmaceuticals Corporation, Florham Park, NJ, 5Novartis Pharma AG, Basel, Switzerland, 6Columbia University College of Physicians & Surgeons, New York, NY
Introduction: Around 20–30% of patients with acromegaly also have hyperprolactinemia, which is associated with infertility and gonadal/sexual dysfunction. Current therapy for these patients involves somatostatin analogues to treat GH/IGF-1 excess and a dopamine agonist to decrease prolactin levels. The objective of this analysis was to assess treatment with pasireotide LAR or octreotide LAR in patients with acromegaly and hyperprolactinemia.

Methods: Patients with active acromegaly (GH >5 µg/L or GH nadir ≥1 µg/L post-OGTT, and IGF-­1 >ULN) who were de novowith a visible adenoma on MRI or medically naïve (no previous medical therapy but prior pituitary surgery) received pasireotide LAR 40 mg/28 days (n=176) or octreotide LAR 20 mg/28 days (n=182) for 12 months; dose titration (to pasireotide LAR 20 or 60 mg or to octreotide LAR 10 or 30 mg) was permitted. This analysis focuses on the efficacy and safety of pasireotide LAR and octreotide LAR in those patients with baseline hyperprolactinemia (prolactin above age- and sex-matched ULN).

Results: Twenty-nine (16.5%) pasireotide LAR and 30 (16.5%) octreotide LAR patients had baseline hyperprolactinemia (mean prolactin levels 83.5 and 55.9 µg/L, respectively). After 12 months, 21/29 (72.4%; 95% CI 52.8, 87.3) pasireotide LAR and 17/30 (56.7%; 95% CI 37.4, 74.5) octreotide LAR patients had normalized prolactin levels; 3/29 (10.3%; 95% CI 2.2, 27.4) and 5/30 (16.7%; 95% CI 5.6, 34.7) had normal IGF-1 and GH <2.5 µg/L; 10/29 (34.5%) and 13/30 (43.3%) had GH <2.5 µg/L; while 7/29 (24.1%) and 8/30 (26.7%) had normal IGF-1, respectively. After 12 months, mean prolactin levels decreased by 60.4% and 39.6%, mean GH decreased by 71.1% and 67.6%, and mean standardized IGF-­1 (x ULN) decreased by 41.1% and 39.6%, respectively, in the pasireotide LAR and octreotide LAR patients. Tumor volume decreased by ~40% in both treatment groups. Pasireotide LAR was well tolerated and most adverse events were mild or moderate in nature; hyperglycemia-related adverse events were more common with pasireotide LAR than octreotide LAR.

Conclusions: In this subset of patients with baseline hyperprolactinemia, pasireotide LAR and octreotide LAR normalized prolactin levels in >70% and ~55% of patients, respectively, normalizing IGF-1 in ~25% and reducing GH levels to <2.5 µg/L in ~35% and ~44% of patients. The observed decrease in tumor volume may be particularly important in patients with hyperprolactinemia caused by compression of the pituitary stalk. Pasireotide LAR and octreotide LAR may be effective treatments for patients with a GH- and prolactin-secreting pituitary adenoma.

Disclosure: AC: , Novartis Pharmaceuticals. MDB: Speaker, Novartis Pharmaceuticals, Speaker, Ipsen, , Ipsen, Committee Member, Novartis Pharmaceuticals, Committee Member, Chiasma, Investigator, Novartis Pharmaceuticals. KH: Employee, Novartis Pharmaceuticals. MR: Employee, Novartis Pharmaceuticals, Employee, Novartis Pharmaceuticals. YC: Employee, Novartis Pharmaceuticals. PUF: Investigator, Novartis Pharmaceuticals, Medical Advisory Board Member, Novartis Pharmaceuticals. Nothing to Disclose: FG

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm

Sources of Research Support: Novartis funded editorial support provided by Mudskipper