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Pasireotide monotherapy in Cushing’s disease: a single-centre experience with 5-year extension of phase III Trial

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Abstract

Purpose

A recent phase III randomized controlled trial (NCT00434148) showed efficacy of pasireotide in the treatment of patients with Cushing’s disease (CD). Patients were invited to participate in an extension phase of the protocol and a subgroup had a sustained response. We report the experience with 4 patients in our center of which 2 full responders have completed 5.5 and 4.25 years of treatment with disease control.

Methods

The trial protocol was described previously. The extension phase consisted of 3-monthly visits with clinical, biochemical, and imaging evaluation and investigator-driven pasireotide titration. Research charts were retrospectively analyzed.

Results

Four patients with persistent CD following pituitary surgery completed the first 6 months of the trial and 3 continued in the next 6 month open-label phase. Two patients with baseline urinary free cortisol (UFC) 5.3–6.7 times the upper limit of normal had a rapid sustained response to pasireotide and entered the extension phase after 12 months. They remain in clinical and biochemical disease remission and 1 patient now only requires 300 μg daily of pasireotide. All 4 patients developed glucose intolerance; however, the two patients in the extension phase were eventually able to discontinue all diabetes pharmacotherapy. Adverse events included second degree atrioventicular block type 1 without QT prolongation in a patient with pre-existing sinus bradycardia, and symptomatic cholelithiasis requiring cholecystectomy in a second patient.

Conclusions

Pasireotide therapy can provide normalization of UFC and of clinical symptoms and signs of CD during up to 5 years of follow-up. This study demonstrates the possible recuperation of normoglycemia after continued use of pasireotide and control of underlying hypercortisolemia. Longer-term monitoring for potential adverse events related to continued use of pasireotide is indicated.

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Acknowledgments

The multicenter Phase III study (B2305, NCT00434148) was funded by Novartis Pharma AG. JMF received fellowship salary support from Fondation du Centre hospitalier de l’Université de Montréal, The Canadian Society of Endocrinology and Metabolism (CSEM), Novartis Canada and Serono Canada. The assistance of Lotte Gaasvik-Blomqvist for retrieval of centralized data, and of Andrés M. Cisneros-Montemayor for preparation of the figures is very much appreciated.

Conflict of interest

IB, SV, HB, LGSM, and AL were co-investigators in the study B2305, NCT00434148 funded by Novartis Pharmaceuticals. AL was an occasional consultant and on the speaker bureau of Novartis Pharmaceuticals. LGSM is a member of consulting committees for Eli Lilly, Amgen, Merck, Novartis, Paladin, Servier, Alliance for better bone health (Warner Chilcott and Sanofi Aventis Canada Inc.) He has received grants from Alliance for better bone health, Amgen, Novartis, Eli Lilly, Servier, Genzyme. He has participated in conferences sponsored by Alliance for better bone health, Amgen, Novartis, Eli Lilly, Servier, Merck, Paladin. JMF has nothing to declare.

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Authors and Affiliations

  1. Division of Endocrinology, Department of Medicine and Research Center, Centre Hospitalier de l’Université de Montréal (CHUM)-Hotel-Dieu, 3850 Saint-Urbain Street, Montreal, QC, H2W 1T8, Canada

    Jessica MacKenzie Feder, Isabelle Bourdeau, Sophie Vallette, Hugues Beauregard, Louis-Georges Ste-Marie & André Lacroix

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  1. Jessica MacKenzie Feder
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  2. Isabelle Bourdeau
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  3. Sophie Vallette
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  4. Hugues Beauregard
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  5. Louis-Georges Ste-Marie
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  6. André Lacroix
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Correspondence to André Lacroix.

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MacKenzie Feder, J., Bourdeau, I., Vallette, S. et al. Pasireotide monotherapy in Cushing’s disease: a single-centre experience with 5-year extension of phase III Trial. Pituitary 17, 519–529 (2014). https://doi.org/10.1007/s11102-013-0539-4

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