Pasireotide treatment significantly reduces tumor volume in patients with Cushing's disease: results from a Phase 3 study

Abstract

Purpose: In the multinational, randomized, double-blind, Phase 3 B2305 study of patients with Cushing's disease (CD; ClinicalTrials.gov identifier NCT00434148), pasireotide substantially decreased urinary-free cortisol (UFC) levels, decreased mean corticotroph tumor volume, and improved clinical signs of disease. The current post hoc analysis further assesses the effects of pasireotide on corticotroph pituitary tumor volume.

Methods: Patients enrolled in the B2305 study had persistent or recurrent CD or newly diagnosed CD but were not surgical candidates. Enrollees were randomized to receive subcutaneous pasireotide, either 600-μg or 900-μg twice daily. Tumor volume was assessed independently at months 6 and 12 by 2 blinded radiologists and compared with baseline value and UFC response.

Results: Of 162 patients enrolled in the trial, 53 had measurable tumor volume data and were included in the post hoc analysis. Reductions in tumor volume were both dose and time dependent. Tumor volume reduction was more frequently observed at month 6 in the 900-μg group (75%) than in the 600-μg group (44%). Similarly, at month 12 (n = 32), tumor volume reduction was observed more frequently in the 900-µg group (89%) than in the 600-µg group (50%). Control of UFC levels was not required for reduction of tumor volume. No relationship was noted between baseline tumor size and change in tumor size.

Conclusions: Measurable decreases in pituitary tumor volume were observed in a large proportion of patients with CD and measurable tumor volume who were enrolled in the trial and treated with subcutaneous pasireotide; this decrease was not correlated with UFC control. CLINICALTRIALS.

Gov identifier: NCT00434148.

Keywords: Corticotroph tumor volume; Cushing’s disease; Pasireotide; Urinary-free cortisol.

Conflict of interest statement

AL has received funding from Novartis Pharmaceuticals Corporation to conduct clinical studies with pasireotide SC and osilodrostat (LCI699) in Cushing’s disease and served occasionally as a consultant, an advisory group member, or a speaker for Novartis, EMD Serono, and Ipsen. FG has served as a consultant, an advisory group member, an investigator, and a speaker for Novartis and Ipsen. JS has served as a lecturer, a researcher, and an advisory group member for Novartis, Ipsen and Pfizer. AK and AMP are employees of Novartis Pharma AG and hold stock options. LJ was employed by Novartis at the time of writing this manuscript but is currently employed by Bristol-Myers Squibb. RP has served as an investigator, a researcher, a consultant, and a speaker for Novartis, Viropharma, Shire, HRA Pharma, and Ipsen.

Figures

Fig. 1

Study design of the Phase 3 study. BID twice daily

Fig. 2

Percentage of tumor volume changes by baseline tumor volume at month 6 in a individual patients treated with pasireotide 900 μg and b individual patients treated with pasireotide 600 μg. UFC urinary-free cortisol. *Indicates full UFC responder. †Indicates UFC partial responder

Fig. 3

Percentage of tumor volume changes by baseline tumor volume at month 6 (black bar) and at month 12 (white bar) in a individual patients treated with pasireotide 600 μg and b individual patients treated with pasireotide 900 μg. UFC urinary-free cortisol. *Indicates full UFC responder. †Indicates UFC partial responder