Pasireotide-LAR and pegvisomant combination in resistant acromegaly: a case series of predominantly mammosomatotroph adenomas.
In treatment-resistant acromegaly, the combination of pasireotide-LAR and pegvisomant may help maintain tumor stability and achieve normal IGF-1 levels, but glucose monitoring is essential due to potential hyperglycemia.
Where it sits
this study against the rest of the pasireotide corpusSummary and findings
This study reports outcomes of six patients with treatment-resistant acromegaly who received a combination of pasireotide-LAR and pegvisomant. The patients, aged 15 to 44 years, maintained tumor stability and achieved normal IGF-1 levels over a median follow-up of 3.3 years. One patient experienced biochemical escape requiring additional surgery.
Abstract
<h4>Purpose</h4>Long-term real-world data on concurrent pasireotide-LAR (PAS) and pegvisomant (PEGV) use in treatment-resistant acromegaly remain limited, especially for mammosomatotroph adenomas in younger adults. We report outcomes of six patients treated with this combination at a single tertiary pituitary center.<h4>Methods</h4>IRB-approved retrospective case series. Baseline and follow-up biochemical, radiological, histopathological, treatment and safety outcomes were captured.<h4>Results</h4>Six patients (5 females, 1 male; age 15 to 44 years) with somatotroph (n = 2) or mammosomatotroph (n = 4) adenomas, all macroadenomas, received PAS (20 to 60 mg every 28 days) plus PEGV (60 to 280 mg/week) over a median of 3.3 years (range 0.5 to 5.9) after lack of disease control post-surgery despite multiple lines of medical therapy. All six maintained tumor stability and achieved normal IGF-1. One had biochemical escape after 9 months of biochemical control requiring a 2nd surgery and radiosurgery. One patient discontinued PEGV after 3 years due to injection site pain, 3 patients developed hyperglycemia in the pre-diabetes range; no hepatotoxicity, acute symptomatic biliary disease, or arrhythmias occurred.<h4>Conclusions</h4>In this series of predominantly mammosomatotroph adenomas in younger adults, combination PAS plus PEGV offers potential durable biochemical control, tumor stability and PEGV dose reduction in treatment-resistant acromegaly. Glucose monitoring during treatment is essential as concomitant use of PEGV does not appear to mitigate PAS-induced glycemic deterioration. Larger prospective studies are needed to better define predictors of response.
Background
This paper addresses the treatment of resistant acromegaly, particularly in patients with mammosomatotroph adenomas. Prior knowledge indicates that managing acromegaly can be challenging, especially after surgical interventions fail. The combination of pasireotide-LAR and pegvisomant has been explored, but long-term data in this specific patient population are limited.
Methods
This is an IRB-approved retrospective case series involving six patients treated at a single tertiary pituitary center. Patients received pasireotide-LAR at doses of 20 to 60 mg every 28 days and pegvisomant at doses of 60 to 280 mg per week. The primary outcomes measured included biochemical, radiological, and treatment safety outcomes over a median follow-up of 3.3 years.
Results
All six patients maintained tumor stability and achieved normal IGF-1 levels. One patient experienced biochemical escape after 9 months, necessitating a second surgery. Three patients developed hyperglycemia in the pre-diabetes range, while no significant adverse events such as hepatotoxicity were reported.
Interpretation
The results suggest that the combination of pasireotide and pegvisomant may provide biochemical control and tumor stability in treatment-resistant acromegaly. However, the small sample size and lack of a control group limit the ability to draw definitive conclusions about clinical significance. The findings highlight the need for glucose monitoring due to potential glycemic deterioration associated with pasireotide.
Key findings
- 6 patients (5 females, 1 male; age 15 to 44 years) with macroadenomas received PAS and PEGV.
- Median treatment duration was 3.3 years (range 0.5 to 5.9 years).
- All six patients maintained tumor stability and achieved normal IGF-1 levels.
- 1 patient had biochemical escape after 9 months requiring a 2nd surgery.
- 3 patients developed hyperglycemia in the pre-diabetes range.
Limitations
- Small n=6 case series.
- Single-center study limits generalizability.
- No control group for comparison.
- Retrospective design may introduce bias.
- Short follow-up duration for long-term outcomes.