SUN-030 - Combination Therapy with Pasireotide LAR and Pegvisomant in Treatment-Resistant Acromegaly: A Case Series

Background: Acromegaly remains challenging to manage in patients (pts) who do not achieve biochemical control with surgery and who are resistant to somatostatin receptor ligands (SRLs) octreotide and lanreotide. Tumor biology factors—including sparse granulation, T2 hyperintensity on MRI, low somatostatin receptor subtype 2 (SSTR2) expression, or reduced expression/mutations of the aryl hydrocarbon receptor–interacting protein (AIP) gene—predict SRL resistance. Pasireotide LAR (PAS-LAR), a multireceptor SRL, may offer improved efficacy in these adenomas, and in combination with pegvisomant (PEGV) can provide synergistic biochemical benefit. Real-world data remain limited.

Methods: IRB-approved retrospective review of pts with persistent acromegaly post-surgery treated with PAS-LAR + PEGV. IGF-1 trends, percent reduction, MRI adenoma response, safety, and treatment duration were assessed.

Results: 5 pts, 4 F, 1M (age 15-44), with somatotroph (1) or mammosomatotroph (4) adenomas, 3 uncontrolled on PAS-LAR, 1 uncontrolled on octreotide LAR+PEGV, and 1 uncontrolled on maximum octreotide LAR, demonstrated significant biochemical improvement on PAS-LAR (40 or 60 mg every 28 days)+ PEGV treated over a median of 3.0 years, range 2.2-5.2 years. Five pts achieved normal or IGF-1 >1.3 ULN . PEGV doses were 60–210 mg/week , with dose reduction observed in 1pt after repeat surgery. One pt had partial initial response with >30% IGF-1 reduction and subsequent normalization after uptitration of both PAS-LAR to 60 mg every 4 weeks and PEGV 140 mg/week, however escaped control after 9 months and underwent repeat surgery and gamma-knife radiation. Tumor control was maintained in all other cases without radiographic progression during follow-up. The regimen was generally well tolerated. Two patients developed worsened hyperglycemia requiring intensification of diabetes therapy, but no cases of hepatotoxicity, gallstones, or arrhythmias occurred. One pt discontinued PEG due to injection site pain after 5 years of use and was lost to follow-up.

Conclusion: Combination PAS-LAR and PEGV is a viable long-term option for treatment-resistant acromegaly, offering meaningful biochemical improvement, maintenance of tumor stability, and potential PEGV dose reduction. Side effects do not seem to be potentiated by combination therapy, but PEGV did not prevent PAS-related hyperglycemia in our pts. Severe acromegaly may (at least temporarily) respond to higher doses of PAS-LAR + PEGV while awaiting repeat surgery and/or radiation. Larger prospective studies are needed to better define predictors of response and long-term outcomes, but this series adds valuable real-world clinical data supporting the targeted use of this combination in highly refractory disease.

*Unless otherwise noted, all abstracts presented at ENDO must not be released to the press or the public until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.*