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.

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

“…Pasireotide, as subcutaneous injection, is formulated as three different immediate-release ampoules, containing 300, 600, and 900 µg doses, with suggestion of a maximum total daily dose of 1,800 µg. Pasireotide has been extensively evaluated in human clinical studies, leading to a large amount of evidence about its efficacy and safety in CD treatment (17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30). The first classical formulation of pasireotide was subcutaneously administered in a twice-daily schedule, with two doses, 600 and 900 µg.…”

“…The evaluation of pasireotide effect on pituitary tumor was firstly reported on the 75 (46%) patients with a measurable tumor at baseline on magnetic resonance imaging (MRI). Tumor shrinkage was observed, both at month 6 and 12, with a mean tumor volume decrease of 5.7% (mean tumor volume increase of 9.3% in the 1,200 μg group and tumor volume decrease of 19% in the 1,800 μg group) and of 28.6% (mean tumor volume decrease of 9.1% in the 1,200 μg group and 43.8% in the 1,800 μg group) ( 18 , 27 ), respectively. In particular, according to a recent post-hoc analysis, considering the 53 patients with measurable tumor volume at both baseline and month 6, a tumor shrinkage ≥25% was observed in 20 (37.7%) patients, whereas, considering the 32 patients with measurable tumor volume at both baseline and month 12, a tumor shrinkage ≥25% was observed in 18 (56.2%) patients ( 27 ).…”

“…Tumor shrinkage was observed, both at month 6 and 12, with a mean tumor volume decrease of 5.7% (mean tumor volume increase of 9.3% in the 1,200 μg group and tumor volume decrease of 19% in the 1,800 μg group) and of 28.6% (mean tumor volume decrease of 9.1% in the 1,200 μg group and 43.8% in the 1,800 μg group) ( 18 , 27 ), respectively. In particular, according to a recent post-hoc analysis, considering the 53 patients with measurable tumor volume at both baseline and month 6, a tumor shrinkage ≥25% was observed in 20 (37.7%) patients, whereas, considering the 32 patients with measurable tumor volume at both baseline and month 12, a tumor shrinkage ≥25% was observed in 18 (56.2%) patients ( 27 ). Noteworthy, both at month 6 and 12, tumor volume reduction was more frequently observed in patients treated with 1,800 μg/day than in patients treated with 1,200 μg/day ( 27 ).…”

“…In particular, according to a recent post-hoc analysis, considering the 53 patients with measurable tumor volume at both baseline and month 6, a tumor shrinkage ≥25% was observed in 20 (37.7%) patients, whereas, considering the 32 patients with measurable tumor volume at both baseline and month 12, a tumor shrinkage ≥25% was observed in 18 (56.2%) patients ( 27 ). Noteworthy, both at month 6 and 12, tumor volume reduction was more frequently observed in patients treated with 1,800 μg/day than in patients treated with 1,200 μg/day ( 27 ). In a report on eight patients, followed-up in one of the main centers participating at the clinical trial, a tumor shrinkage >25% was observed in five (62.5%) patients after 6 months and in the totality (100%) of patients after 12 months, with a mean tumor shrinkage of 42.4 and 61.6%, respectively, and tumor mass disappearance in one (14.3%) case after 12 months of treatment ( 23 ).…”

Recurrence after pituitary surgery in adult Cushing’s disease: a systematic review on diagnosis and treatment

“…Pasireotide is more effective in patients with mild or moderate hypercortisolism, with urinary free cortisol levels of up to two-times the normal range reaching control rates in~40% [76]. Pasireotide treatment also leads to reduction of tumor volume [77]. Cabergoline is effective in up to 40% of patients, but 22% of patients escaped from remission over the long-term [78].…”