PMID-29032078 – Once-Monthly Pasireotide LAR in Cushing Disease
Lacroix A, Gu F, Gallardo W, et al. Efficacy and safety of once-monthly pasireotide in Cushing's disease: a 12 month clinical trial. Lancet Diabetes Endocrinol. 2018;6(1):17-26.
Quick Reference
| Property | Value |
|---|---|
| PMID | 29032078 |
| DOI | 10.1016/S2213-8587(17)30326-1 |
| Year | 2018 |
| Journal | Lancet Diabetes & Endocrinology |
| Study Type | RCT |
| Evidence Level | I |
| Sample | 150 patients with Cushing's disease |
| Peptide(s) Studied | Pasireotide |
Key Findings
- UFC normalization achieved in 41.9% of the 10 mg group and 40.8% of the 30 mg group at month 7 (primary endpoint)
- Rapid reduction in UFC: median decreases evident by month 1-2
- Significant clinical improvements in body weight, waist circumference, blood pressure, and facial rubor
- Tumor volume decreased in both dose groups
- Hyperglycemia-related AEs occurred in 76% of patients; mean HbA1c increased by ~1%
- Once-monthly intramuscular formulation offered improved convenience over twice-daily subcutaneous pasireotide
Study Design
Multicenter, randomized, double-blind, Phase III trial (G2304, NCT01374906). Adults with persistent or recurrent Cushing's disease (or de novo patients not surgical candidates) were randomized 1:1 to pasireotide LAR 10 mg or 30 mg IM every 28 days for 12 months. Dose uptitration was permitted at month 4 if UFC was not normalized. Primary endpoint: UFC normalization at month 7.
Limitations
- No placebo arm (ethical constraints in Cushing's disease)
- Both arms received active treatment; no dose-response advantage of 30 mg over 10 mg was demonstrated
- High rate of hyperglycemia limits applicability in patients with pre-existing diabetes
- Enrollment challenges due to disease rarity
Clinical Relevance
This trial established the long-acting monthly formulation (pasireotide LAR) as effective for Cushing's disease, providing a more convenient dosing schedule compared to the original twice-daily subcutaneous formulation. The ~40% normalization rate at month 7 is clinically meaningful for a disease with limited pharmacological options. The persistent hyperglycemia risk reinforces that all patients on pasireotide require glucose monitoring and often concomitant antidiabetic management.
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#research #RCT #pasireotide #evidence-level-I