Long-term treatment of Cushing’s disease with pasireotide: 5-year results from an open-label extension study of a Phase III trial

Abstract

BackgroundTreating hypercortisolism in patients with Cushing’s disease after failed surgery often requires chronic medication, underlining the need for therapies with favourable long-term efficacy and safety profiles.MethodsIn a randomised, double-blind study, 162 adult patients with persistent/recurrent or de novo Cushing’s disease received pasireotide. Patients with mean urinary free cortisol at/below the upper limit of normal or clinical benefit at month 12 could continue receiving pasireotide during an open-ended, open-label phase, the outcomes of which are described herein.ResultsSixteen patients received 5 years of pasireotide treatment. Among these, median (95% confidence interval) percentage change from baseline in mean urinary free cortisol was −82.6% (−89.0, −41.9) and −81.8% (−89.8, −67.4) at months 12 and 60. Eleven patients had mean urinary free cortisol ≤ upper limit of normal at month 60. Improvements in clinical signs were sustained during long-term treatment. The safety profile of pasireotide at 5 years was similar to that reported after 12 months. Fifteen of 16 patients experienced a hyperglycaemia-related adverse event; glycated haemoglobin levels were stable between months 6 and 60. Adverse events related to hyperglycaemia, bradycardia, gallbladder/biliary tract, and liver safety were most likely to first occur by month 6; adverse event severity did not tend to worsen over time.ConclusionsThis represents the longest prospective trial of a medical therapy for Cushing’s disease to date. A subset of patients treated with pasireotide maintained biochemical and clinical improvements for 5 years, with no new safety signals emerging. These data support the use of pasireotide as an effective long-term therapy for some patients with Cushing’s disease.

The treatment with pasireotide in Cushing’s disease: effect of long-term treatment on clinical picture and metabolic profile and management of adverse events in the experience of a single center

“…In line with the previous evidence, the observed improvements were similar in FC, PC, and UC patients, confirming that pasireotide effects on clinical picture and metabolic profile were present also in patients with cortisol reduction, although mostly evident in patients with complete normalization of cortisol secretion. Interestingly, these results seem to confirm not only data of the phase III study, but also data reported in different studies, mainly small series or case reports [23][24][25][26][27][28][29][30], published during the last years, that have documented improvements in signs and symptoms [23][24][25][26][27][28], BW [22,23,[26][27][28][29], WC [26][27][28][29], blood pressure [22,23,[25][26][27][28][29][30], and lipid profile [28].…”

“…Notably, in these large experiences, UFC reduction was accompanied by improvements in symptoms and signs as well as in metabolic profile and comorbidities of CD, also maintained during long-term treatment [10][11][12]23]. Facial rubor, supraclavicular and dorsal fat pads, and bruising improved, whereas BW, BMI, WC, blood pressure, total and LDL cholesterol were significantly reduced, as well as depression and QoL scores improved [10][11][12].…”

“…Regardless of dose increase, full or partial disease control was obtained in 34.2% (600 μg bid) and 41.3% (900 μg bid) of patients after 6 months, and in 29.3% (600 μg) and 27.5% (900 μg) of patients after 12 months [10]. More recently, pasireotide was reported to control UFC levels over 24 months of treatment in 20 (34.5%) of 58 patients who entered the extension phase III study [12], and over 60 months in 11 (68.8%) of 16 patients who received 5 years of pasireotide treatment [23].…”

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

“…14 Cardiovascular disease is the leading cause of death in patients with CD. 14 Cardiovascular disease is the leading cause of death in patients with CD.…”

“…These results support the long-term efficacy of pasireotide and are consistent with findings from a Phase III study, in which 69% (n = 11/16) of ongoing patients had controlled mUFC after 5 years of twice-daily, subcutaneous pasireotide therapy. 14 Note: AEs are sorted in descending order of events during the extension. Patients who experienced an AE during the core study (months 0-12) and the extension (after month 12) are counted in both columns.…”