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

Abstract

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.

Medical Treatment of Cushing's Disease: An Overview of the Current and Recent Clinical Trials

“…Noteworthy, 27 (64.3%) of 42 patients with controlled mUC at 12 months, at the end of the core study and starting of extension, maintained mUC normalization at 24 months. Moreover, considering a subgroup of 18 patients reaching 36 months of continuative treatment, mUC normalization was reached in 13 (72.2%) patients ( 34 ). A decrease in body weight, waist circumference, and blood pressure was sustained during the extension, together with the improvement in quality of life.…”

“…In a subsequent, extension study to 36 months of the phase III clinical trial, 81 CD patients were treated with pasireotide LAR for a median follow-up of 23.9 months ( 34 ). After 24 months of treatment at doses ranging from 5 to 40 mg every 4 weeks, pasireotide LAR induced mUC normalization in 38 (46.9%) patients, with 12 (14.8%) patients requiring a dose up-titration during the 12 months of extension after the core study.…”

“…Of the 35 patients with a measurable tumor at MRI of core baseline and month 24, tumor shrinkage ≥20% was observed in 12 (34.3%) patients. The most frequently reported AEs were hyperglycemia (23.5%), nasopharyngitis (19.8%), and cholelithiasis (18.5%) ( 34 ). Hyperglycemia-related AEs occurred in 32 (39.5%) patients ( 34 ).…”

“…The most frequently reported AEs were hyperglycemia (23.5%), nasopharyngitis (19.8%), and cholelithiasis (18.5%) ( 34 ). Hyperglycemia-related AEs occurred in 32 (39.5%) patients ( 34 ). Treatment discontinuation occurred in 42 (51.8%) patients, because of AEs in eight (9.9%) and lack of efficacy in 12 (14.8%) patients ( 34 ).…”

Somatostatin Analogs in Clinical Practice: A Review

“…Normal UFC was present in 51.9%, 16.0%, and 53.1% at extension baseline, 36th month, and last assessment, respectively. Diabetes was present in 81.5% and 88.9% at extension baseline and last assessment, respectively [64].…”