SAT-083 - Effect of GLP-1 Receptors Agonists on Progression Free Survival in Patients with Well Differentiated Neuroendocrine Tumors.

The use of GLP-1 receptor agonists (GLP-1RA) is steadily increasing in the US, yet their effects on neuroendocrine tumors (NET) remain unclear. While GLP-1RA are currently contraindicated patients with medullary thyroid cancer, preclinical studies have suggested that other primary NETs with GLP1R expression may have increased growth in response to GLP-1RA. This study explores GLP-1RA use amongst patients with NETs in a retrospective data set.
A retrospective cohort study was conducted at a large cancer center in New York City to evaluate patients with NETs, with and without GLP-1RA exposure. The study was IRB-approved, and patients who attended the cancer center between January 2023 and March 2024 were included. Exclusion criteria included high-grade neuroendocrine carcinoma, poorly differentiated neuroendocrine carcinoma, pheochromocytoma, and paragangliomas.
Among 588 patients with NETs, 45 (8%) had exposure to GLP-1RA, including 19 (42%) who received dual GIP/GLP-1RAs. The median age was 60 years (52-71); 66% were female and 68% were White. GLP-1RA were mostly started for diabetes (71%). Median duration of GLP-1RA exposure was 838 days (range 412–1,607), including 14 patients (31%) who initiated therapy prior to NET diagnosis (median exposure 393 days; range 151–1,596). At the time of data collection, 17 patients (37%) had discontinued GLP-1RA, and 19 (42%) had received lanreotide, with a median progression-free survival of 757 days (range 321–1,253).
Disease progression occurred in 8 patients (17%). Among those who progressed, 3 (37%) were receiving GLP-1RA at the time of progression, with a median A1c of 7.8% (range 6.4–9.4) and median GLP-1RA exposure of 743 days (range 141–1,067). Pancreatic primary tumors were present in 4 patients (50%), 7 (87%) had been treated with lanreotide, and 3 (37%) had functional tumor syndromes. In univariable Firth penalized Cox regression analyses, GLP-1RA exposure prior to NET diagnosis was not significantly associated with the risk of progression (HR 0.26, 95% CI 0.05–1.34; p = 0.096), nor was dual GIP/GLP-1RA therapy (HR 0.33, 95% CI 0.035–1.52; p = 0.17). Age (HR per year 1.03, 95% CI 0.96–1.11; p = 0.45) and functional hormonal syndrome (HR 1.80, 95% CI 0.42–6.80; p = 0.40) were also not significantly associated with progression. In contrast, discontinuation of GLP-1RA therapy (HR 4.57, 95% CI 1.19–20.13; p = 0.028) was significantly associated with increased hazard of progression

Of our total 588 patients with NET in this study, only a small percentage (8%) had been treated with GLP-1RA, which is potentially due to the lack of data in its use in these patients.
Due to the small number of events, the exploratory analysis design, univariate analysis, and retrospective nature of the cohort all results should be interpreted cautiously.

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