Long-term efficacy and safety of subcutaneous pasireotide alone or in combination with cabergoline in Cushing’s disease
ObjectiveThis study evaluated short- and long-term efficacy and safety of the second-generation somatostatin receptor ligand pasireotide alone or in combination with dopamine agonist cabergoline in patients with Cushing’s disease (CD).Study designThis is an open-label, multicenter, non-comparative,...
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| Format: | Article |
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Frontiers Media S.A.
2023-10-01
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| Series: | Frontiers in Endocrinology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fendo.2023.1165681/full |
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| author | Richard A. Feelders Maria Fleseriu Pinar Kadioglu Marie Bex Deyanira González-Devia Cesar Luiz Boguszewski Dilek Gogas Yavuz Heather Patino Alberto M. Pedroncelli Alberto M. Pedroncelli Ricardo Maamari Arghya Chattopadhyay Beverly M. K. Biller Rosario Pivonello |
| author_facet | Richard A. Feelders Maria Fleseriu Pinar Kadioglu Marie Bex Deyanira González-Devia Cesar Luiz Boguszewski Dilek Gogas Yavuz Heather Patino Alberto M. Pedroncelli Alberto M. Pedroncelli Ricardo Maamari Arghya Chattopadhyay Beverly M. K. Biller Rosario Pivonello |
| author_sort | Richard A. Feelders |
| collection | DOAJ |
| description | ObjectiveThis study evaluated short- and long-term efficacy and safety of the second-generation somatostatin receptor ligand pasireotide alone or in combination with dopamine agonist cabergoline in patients with Cushing’s disease (CD).Study designThis is an open-label, multicenter, non-comparative, Phase II study comprising 35-week core phase and an optional extension phase. All patients started with pasireotide, and cabergoline was added if cortisol remained elevated. Eligible patients had active CD, with or without prior surgery, were pasireotide naïve at screening or had discontinued pasireotide for reasons other than safety. Primary endpoint was proportion of patients with a mean urinary free cortisol (mUFC) level not exceeding the upper limit of normal (ULN) at week 35 with missing data imputed using last available post-baseline assessments.ResultsOf 68 patients enrolled, 26 (38.2%) received pasireotide monotherapy and 42 (61.8%) received pasireotide plus cabergoline during the core phase. Thirty-four patients (50.0%; 95% CI 37.6–62.4) achieved the primary endpoint, of whom 17 (50.0%) received pasireotide monotherapy and 17 (50.0%) received combination therapy. Proportion of patients with mUFC control remained stable during the extension phase up to week 99. Treatment with either mono or combination therapy provided sustained improvements in clinical symptoms of hypercortisolism up to week 99. Hyperglycemia and nausea (51.5% each), diarrhea (44.1%) and cholelithiasis (33.8%) were the most frequent adverse events.ConclusionAddition of cabergoline in patients with persistently elevated mUFC on maximum tolerated doses of pasireotide is an effective and well-tolerated long-term strategy for enhancing control of hypercortisolism in some CD patients.Clinical trial registrationhttps://clinicaltrials.gov/ct2/show/NCT01915303, identifier NCT01915303. |
| first_indexed | 2024-03-11T19:11:14Z |
| format | Article |
| id | doaj.art-86214c58d1f74f27941ac5fba59ebff5 |
| institution | Directory Open Access Journal |
| issn | 1664-2392 |
| language | English |
| last_indexed | 2024-03-11T19:11:14Z |
| publishDate | 2023-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Endocrinology |
| spelling | doaj.art-86214c58d1f74f27941ac5fba59ebff52023-10-09T12:46:02ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922023-10-011410.3389/fendo.2023.11656811165681Long-term efficacy and safety of subcutaneous pasireotide alone or in combination with cabergoline in Cushing’s diseaseRichard A. Feelders0Maria Fleseriu1Pinar Kadioglu2Marie Bex3Deyanira González-Devia4Cesar Luiz Boguszewski5Dilek Gogas Yavuz6Heather Patino7Alberto M. Pedroncelli8Alberto M. Pedroncelli9Ricardo Maamari10Arghya Chattopadhyay11Beverly M. K. Biller12Rosario Pivonello13Department of Internal Medicine, Division of Endocrinology, Erasmus Medical Center, Rotterdam, NetherlandsPituitary Center, Departments of Medicine and Neurological Surgery, Oregon Health & Science University, Portland, OR, United StatesDivision of Endocrinology, Metabolism and Diabetes, Cerrahpasa Medical Faculty, Istanbul University - Cerrahpasa, Istanbul, TürkiyeDepartment of Endocrinology, University Hospitals Leuven, Leuven, BelgiumDepartamento de Medicina Interna, Sección de Endocrinologia, Hospital Universitario Fundación Santa Fé de Bogotá, Bogota, ColombiaDepartment of Internal Medicine, Endocrine Division (SEMPR), Federal University of Paraná, Curitiba, Parana, BrazilSection of Endocrinology and Metabolism, Marmara University School of Medicine, Department of Internal Medicine, Division of Endocrinology and Metabolism, Istanbul, TürkiyeGlobal Medical Affairs, Novartis Pharmaceuticals Corporation, East Hanover, NJ, United StatesRecordati AG, Basel, Switzerland0Global Medical Affairs, Novartis Pharma AG, Basel, SwitzerlandGlobal Medical Affairs, Novartis Pharmaceuticals Corporation, East Hanover, NJ, United States1Global Medical Affairs, Novartis Healthcare Private Limited, Hyderabad, Telangana, India2Neuroendocrine & Pituitary Tumor Clinical Center, Massachusetts General Hospital, Boston, MA, United States3Dipartimento di Medicina Clinica e Chirurgia, Sezione di Endocrinologia, Università Federico II di Napoli, Naples, ItalyObjectiveThis study evaluated short- and long-term efficacy and safety of the second-generation somatostatin receptor ligand pasireotide alone or in combination with dopamine agonist cabergoline in patients with Cushing’s disease (CD).Study designThis is an open-label, multicenter, non-comparative, Phase II study comprising 35-week core phase and an optional extension phase. All patients started with pasireotide, and cabergoline was added if cortisol remained elevated. Eligible patients had active CD, with or without prior surgery, were pasireotide naïve at screening or had discontinued pasireotide for reasons other than safety. Primary endpoint was proportion of patients with a mean urinary free cortisol (mUFC) level not exceeding the upper limit of normal (ULN) at week 35 with missing data imputed using last available post-baseline assessments.ResultsOf 68 patients enrolled, 26 (38.2%) received pasireotide monotherapy and 42 (61.8%) received pasireotide plus cabergoline during the core phase. Thirty-four patients (50.0%; 95% CI 37.6–62.4) achieved the primary endpoint, of whom 17 (50.0%) received pasireotide monotherapy and 17 (50.0%) received combination therapy. Proportion of patients with mUFC control remained stable during the extension phase up to week 99. Treatment with either mono or combination therapy provided sustained improvements in clinical symptoms of hypercortisolism up to week 99. Hyperglycemia and nausea (51.5% each), diarrhea (44.1%) and cholelithiasis (33.8%) were the most frequent adverse events.ConclusionAddition of cabergoline in patients with persistently elevated mUFC on maximum tolerated doses of pasireotide is an effective and well-tolerated long-term strategy for enhancing control of hypercortisolism in some CD patients.Clinical trial registrationhttps://clinicaltrials.gov/ct2/show/NCT01915303, identifier NCT01915303.https://www.frontiersin.org/articles/10.3389/fendo.2023.1165681/fullsomatostatinpasireotidecabergolineCushing’s diseasehypercortisolism |
| spellingShingle | Richard A. Feelders Maria Fleseriu Pinar Kadioglu Marie Bex Deyanira González-Devia Cesar Luiz Boguszewski Dilek Gogas Yavuz Heather Patino Alberto M. Pedroncelli Alberto M. Pedroncelli Ricardo Maamari Arghya Chattopadhyay Beverly M. K. Biller Rosario Pivonello Long-term efficacy and safety of subcutaneous pasireotide alone or in combination with cabergoline in Cushing’s disease Frontiers in Endocrinology somatostatin pasireotide cabergoline Cushing’s disease hypercortisolism |
| title | Long-term efficacy and safety of subcutaneous pasireotide alone or in combination with cabergoline in Cushing’s disease |
| title_full | Long-term efficacy and safety of subcutaneous pasireotide alone or in combination with cabergoline in Cushing’s disease |
| title_fullStr | Long-term efficacy and safety of subcutaneous pasireotide alone or in combination with cabergoline in Cushing’s disease |
| title_full_unstemmed | Long-term efficacy and safety of subcutaneous pasireotide alone or in combination with cabergoline in Cushing’s disease |
| title_short | Long-term efficacy and safety of subcutaneous pasireotide alone or in combination with cabergoline in Cushing’s disease |
| title_sort | long term efficacy and safety of subcutaneous pasireotide alone or in combination with cabergoline in cushing s disease |
| topic | somatostatin pasireotide cabergoline Cushing’s disease hypercortisolism |
| url | https://www.frontiersin.org/articles/10.3389/fendo.2023.1165681/full |
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