ECE2018 Guided Posters Pituitary Clinical (12 abstracts)
Long-term efficacy and safety of once-monthly pasireotide in patients with Cushing’s disease: A Phase III extension study
Maria Fleseriu 1 , Stephan Petersenn 2 , Beverly M K Biller 3 , Pinar Kadioglu 4 , Christophe De Block 5 , Guy T’Sjoen 6 , Marie C Vantyghem 7 , Libuse Tauchmanova 8 , Shoba Ravichandran 9 , Michael Roughton 8 , André Lacroix 10 & John Newell-Price 11
1Oregon Health & Science University, Portland, Oregon, USA; 2ENDOC Center for Endocrine Tumors, Hamburg, Germany; 3Massachussetts General Hospital, Boston, Massachussetts, USA; 4Pituitary Center, Istanbul University, Istanbul, Turkey; 5Department of Endocrinology, Diabetology and Metabolism, Antwerp University Hospital, Antwerp, Belgium; 6Department of Endocrinology and Center for Sexology and Gender, Ghent University Hospital, Ghent, Belgium; 7Endocrinology, Diabetology and Metabolism, CHU Lille, Lille, France; 8Novartis Pharma AG, Basel, Switzerland; 9Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, USA; 10Centre hospitalier de l’Université de Montréal, Montreal, Quebec, Canada; 11University of Sheffield, Sheffield, UK
Introduction: The 12-month results of a multicentre, double-blind, Phase III study showing the efficacy and safety of a monthly, long-acting formulation of pasireotide in Cushing’s disease (CD) patients have been reported previously (Lacroix et al. Lancet Diabetes Endocrinol 2018). The results of the extension phase of this study are reported here.
Methods: Patients (n=150) with persistent/recurrent or de novo CD and mean urinary free cortisol (mUFC) 1.5–5× the upper limit of normal (ULN) were randomized to monthly pasireotide 10mg (n=74) or 30 mg (n=76). Up-titration was permitted at month (M) 4, M7, M9, or M12. Patients could enter an optional, open-ended extension if they had mUFC≤ULN at M12 and/or experienced significant clinical benefit in the investigator’s opinion. Investigators and patients were unblinded after the M12 analyses were completed. Data from both dose groups were pooled for this analysis.
Results: Of 104 patients who completed the core study, 81 entered the extension. Median (range) exposure for patients who entered the extension was 23.9 (12.0–55.3) months. Of patients who entered the extension and had a valid mUFC assessment at the given time point, a controlled response (mUFC≤ULN) occurred in 42/81 (51.9%; 95%CI: 40.5,63.1) patients at M12, 38/58 (65.5%; 95%CI: 51.9,77.5) patients at M24, and 13/18 (72.2%; 95%CI: 46.5,90.3) patients at M36. Median (range) change from baseline in mUFC was −51.9% (−98.7,422.3) at M12, −64.1% (−97.8,356.0) at M24, and −68.3% (−99.2,−12.7) at M36. A ≥20% tumour-volume reduction from baseline was seen in 25/38 (65.8%) patients at M24 and 9/14 (64.3%) patients at M36; 10/14 (71.4%) and 4/4 (100%) patients with a pituitary macroadenoma (maximum diameter ≥10 mm) at baseline had a ≥20% reduction at M24 and M36, respectively. Improvements in clinical signs, including systolic/diastolic blood pressure and weight, were seen at M24 and M36. The safety profile of pasireotide was consistent with previous experience, with no new safety signals detected during the extension. Median (range) change from baseline in HbA1c was 0.9% (0.8,1.2) at M24 and 0.8% (−0.2,2.2) at M36. After the M12 data cut-off, grade 3 adverse events (hyperglycaemia, hypertension, hypoglycaemia) were reported in three more patients; no grade 4 adverse events were reported.
Conclusion: Long-term treatment with long-acting pasireotide provided sustained biochemical and clinical improvements and reduced tumour volume, with no new safety signals emerging. These data support the use of long-acting pasireotide as an effective long-term treatment for some patients with CD.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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