Efficacy and safety of once-monthly pasireotide in Cushing's disease: a 12 month clinical trial

Lacroix, André; Gu, Feng; Gallardo, Wilson; Pivonello, Rosario; Yu, Yerong; Witek, Przemysław; Boscaro, Marco; Salvatori, Roberto; Yamada, Masanobu; Tauchmanovà, Libuse; Roughton, Michael; Ravichandran, Shoba; Petersenn, Stephan; Biller, Beverly M. K.; Newell‐Price, John; Arnaldi, Giorgio; Asha, Hesarghatta Shyamasunder; Bandgar, Tushar; Barkan, Ariel; Biering, H.; Bex, Marie; Bolanowski, Marek; Bronstein, Marcello D.; Brue, Thierry; Bruera, Darío; Cavagnini, Francesco; Çömlekçi, Abdurrahman; Block, Christophe De; Delibaşı, Tuncay; Fajardo‐Montañana, Carmen; Feelders, Richard A; Fleseriu, Maria; Gadelha, Mônica R.; Geer, Eliza B.; Heaney, Anthony P.; Houde, Ghislaine; Ichihara, Atsuhiro; Imran, Syed Ali; Ioachimescu, Adriana G.; Kadıoğlu, Pınar; Li, Yiming; Loli, Paola; Nishiyama, Mitsuru; Rozhinskaya, Ludmila; Ruchała, Marek; Saitoh, Youichi; Schöfl, Christof; Schopohl, Jochen; Shimatsu, Akira; Shimizu, Chisato; Snabboon, Thiti; Snyder, Peter J.; Suzaki, Noriyuki; Tabarin, Antoine; Takahashi, Yutaka; Britto, Susana Tara; T’Sjoen, Guy; Vantyghem, Marie-Christine; Velkeniers, Brigitte; Webb, Susan M.; Yamada, Shozo

doi:10.1016/s2213-8587(17)30326-1

Cited by 130 publications

(113 citation statements)

References 25 publications

Supporting

Mentioning

101

Contrasting

Unclassified

Order By: Relevance

“…In One patient died from cardiac failure during the extension. This death was previously reported as part of the core study analysis, 11 as the patient died before unblinding of the core study. The death was not suspected to be study drug related.…”

Section: Change In Clinical Signs Of Hypercortisolism and Health-rementioning

confidence: 81%

“…11 Patients who entered the extension continued long-acting pasireotide (without interruption) at the same dose that they received at month 12. 11 Patients who entered the extension continued long-acting pasireotide (without interruption) at the same dose that they received at month 12.…”

Section: Methodsmentioning

confidence: 99%

“…During the core study, adults with confirmed CD and mUFC of 1.5-5.0 × ULN were randomized to double-blind pasireotide 10 or 30 mg every 28 days; dose titration was permitted based on efficacy/tolerability. 11 Patients who entered the extension continued long-acting pasireotide (without interruption) at the same dose that they received at month 12. Pasireotide dose could be increased (5 to 10 mg, 10 to 20 mg, 30 to 40 mg every 28 days) if mUFC > 1.0 × ULN, providing there was an interval of ≥3 months since last increase.…”

Section: Methodsmentioning

confidence: 99%

“…11 Patients could enter the extension if they satisfied the following criteria at the end of the core study: mean urinary free cortisol (mUFC; mean of three 24-hour samples collected within 2 weeks) not exceeding the upper limit of normal (ULN; 166.5 nmol/24 h) and/ or considered by the investigator to be receiving significant clinical benefit from long-acting pasireotide; demonstrated acceptable tolerability of pasireotide during the core study; and provided consent to participate in the extension. 11 Patients could enter the extension if they satisfied the following criteria at the end of the core study: mean urinary free cortisol (mUFC; mean of three 24-hour samples collected within 2 weeks) not exceeding the upper limit of normal (ULN; 166.5 nmol/24 h) and/ or considered by the investigator to be receiving significant clinical benefit from long-acting pasireotide; demonstrated acceptable tolerability of pasireotide during the core study; and provided consent to participate in the extension.…”

Section: Patientsmentioning

confidence: 99%

“…This was an optional, open-label extension to a 12-month Phase III core study. 11 Patients could enter the extension if they satisfied the following criteria at the end of the core study: mean urinary free cortisol (mUFC; mean of three 24-hour samples collected within 2 weeks) not exceeding the upper limit of normal (ULN; 166.5 nmol/24 h) and/ or considered by the investigator to be receiving significant clinical benefit from long-acting pasireotide; demonstrated acceptable tolerability of pasireotide during the core study; and provided consent to participate in the extension.…”

Section: Patientsmentioning

confidence: 99%

See 4 more Smart Citations

Long‐term efficacy and safety of once‐monthly pasireotide in Cushing's disease: A Phase III extension study

Fleseriu

Petersenn²,

Biller

et al. 2019

Clinical Endocrinology

Self Cite

View full text Add to dashboard Cite

ObjectivesMany patients with Cushing's disease (CD) require chronic pharmacotherapy to control their hypercortisolism. We evaluated the efficacy and safety of long‐acting pasireotide during a long‐term extension study in patients with CD.DesignOpen‐label extension to a 12‐month Phase III study of long‐acting pasireotide in CD (N = 150; NCT01374906).PatientsPatients with mean urinary free cortisol (mUFC) ≤ upper limit of normal (ULN) or receiving clinical benefit at core study end could continue long‐acting pasireotide during the extension.ResultsEighty‐one of 150 (54.0%) enrolled patients entered the extension. Median overall exposure to pasireotide at study end was 23.9 months; 39/81 (48.1%) patients completed the extension (received ≥ 12 months’ treatment during the extension and could transit to a separate pasireotide safety study). mUFC was ≤ULN in 42/81 (51.9%), 13/81 (16.0%) and 43/81 (53.1%) patients at extension baseline, month (M) 36 and last assessment. Median mUFC remained within normal limits. Median late‐night salivary cortisol was 2.6 × ULN at core baseline and 1.3 × ULN at M36. Clinical improvements were sustained over time. Forty‐two (51.9%) patients discontinued during the extension: 25 (30.9%) before M24 and 17 (21.0%) after M24. Hyperglycaemia‐related AEs occurred in 39.5% of patients. Mean fasting glucose (FPG) and glycated haemoglobin (HbA1c) were stable during the extension, with antidiabetic medication initiated/escalated in some patients. Sixty‐six (81.5%) and 71 (88.9%) patients were classified as having diabetes (HbA1c ≥ 6.5%, FPG ≥ 7.0 mmol/L, antidiabetic medication use, or history of diabetes) at extension baseline and last assessment.ConclusionsLong‐acting pasireotide provided sustained biochemical and clinical improvements, with no new safety signals emerging, supporting its use as an effective long‐term therapy for CD.

show abstract

Section: Change In Clinical Signs Of Hypercortisolism and Health-rementioning

confidence: 81%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Patientsmentioning

confidence: 99%

Section: Patientsmentioning

confidence: 99%

See 3 more Smart Citations

Long‐term efficacy and safety of once‐monthly pasireotide in Cushing's disease: A Phase III extension study

Fleseriu

Petersenn²,

Biller

et al. 2019

Clinical Endocrinology

Self Cite

View full text Add to dashboard Cite

show abstract

Cushing Syndrome

Reincke

Fleseriu

2023

JAMA

Self Cite

View full text Add to dashboard Cite

ImportanceCushing syndrome is defined as a prolonged increase in plasma cortisol levels that is not due to a physiological etiology. Although the most frequent cause of Cushing syndrome is exogenous steroid use, the estimated incidence of Cushing syndrome due to endogenous overproduction of cortisol ranges from 2 to 8 per million people annually. Cushing syndrome is associated with hyperglycemia, protein catabolism, immunosuppression, hypertension, weight gain, neurocognitive changes, and mood disorders.ObservationsCushing syndrome characteristically presents with skin changes such as facial plethora, easy bruising, and purple striae and with metabolic manifestations such as hyperglycemia, hypertension, and excess fat deposition in the face, back of the neck, and visceral organs. Cushing disease, in which corticotropin excess is produced by a benign pituitary tumor, occurs in approximately 60% to 70% of patients with Cushing syndrome due to endogenous cortisol production. Evaluation of patients with possible Cushing syndrome begins with ruling out exogenous steroid use. Screening for elevated cortisol is performed with a 24-hour urinary free cortisol test or late-night salivary cortisol test or by evaluating whether cortisol is suppressed the morning after an evening dexamethasone dose. Plasma corticotropin levels can help distinguish between adrenal causes of hypercortisolism (suppressed corticotropin) and corticotropin-dependent forms of hypercortisolism (midnormal to elevated corticotropin levels). Pituitary magnetic resonance imaging, bilateral inferior petrosal sinus sampling, and adrenal or whole-body imaging can help identify tumor sources of hypercortisolism. Management of Cushing syndrome begins with surgery to remove the source of excess endogenous cortisol production followed by medication that includes adrenal steroidogenesis inhibitors, pituitary-targeted drugs, or glucocorticoid receptor blockers. For patients not responsive to surgery and medication, radiation therapy and bilateral adrenalectomy may be appropriate.Conclusions and RelevanceThe incidence of Cushing syndrome due to endogenous overproduction of cortisol is 2 to 8 people per million annually. First-line therapy for Cushing syndrome due to endogenous overproduction of cortisol is surgery to remove the causative tumor. Many patients will require additional treatment with medications, radiation, or bilateral adrenalectomy.

show abstract

Diagnosis and Management of Pituitary Adenomas

Tritos

Miller

2023

JAMA

102

View full text Add to dashboard Cite

ImportancePituitary adenomas are neoplasms of the pituitary adenohypophyseal cell lineage and include functioning tumors, characterized by the secretion of pituitary hormones, and nonfunctioning tumors. Clinically evident pituitary adenomas occur in approximately 1 in 1100 persons.ObservationsPituitary adenomas are classified as either macroadenomas (≥10 mm) (48% of tumors) or microadenomas (&lt;10 mm). Macroadenomas may cause mass effect, such as visual field defects, headache, and/or hypopituitarism, which occur in about 18% to 78%, 17% to 75%, and 34% to 89% of patients, respectively. Thirty percent of pituitary adenomas are nonfunctioning adenomas, which do not produce hormones. Functioning tumors are those that produce an excess of normally produced hormones and include prolactinomas, somatotropinomas, corticotropinomas, and thyrotropinomas, which produce prolactin, growth hormone, corticotropin, and thyrotropin, respectively. Approximately 53% of pituitary adenomas are prolactinomas, which can cause hypogonadism, infertility, and/or galactorrhea. Twelve percent are somatotropinomas, which cause acromegaly in adults and gigantism in children, and 4% are corticotropinomas, which secrete corticotropin autonomously, resulting in hypercortisolemia and Cushing disease. All patients with pituitary tumors require endocrine evaluation for hormone hypersecretion. Patients with macroadenomas additionally require evaluation for hypopituitarism, and patients with tumors compressing the optic chiasm should be referred to an ophthalmologist for formal visual field testing. For those requiring treatment, first-line therapy is usually transsphenoidal pituitary surgery, except for prolactinomas, for which medical therapy, either bromocriptine or cabergoline, is usually first line.Conclusions and RelevanceClinically manifest pituitary adenomas affect approximately 1 in 1100 people and can be complicated by syndromes of hormone excess as well as visual field defects and hypopituitarism from mass effect in larger tumors. First-line therapy for prolactinomas consists of bromocriptine or cabergoline, and transsphenoidal pituitary surgery is first-line therapy for other pituitary adenomas requiring treatment.

show abstract

Efficacy and safety of once-monthly pasireotide in Cushing's disease: a 12 month clinical trial

Cited by 130 publications

References 25 publications

Long‐term efficacy and safety of once‐monthly pasireotide in Cushing's disease: A Phase III extension study

Long‐term efficacy and safety of once‐monthly pasireotide in Cushing's disease: A Phase III extension study

Cushing Syndrome

Diagnosis and Management of Pituitary Adenomas

Contact Info

Product

Resources

About