NANETS2025 18th Annual Multidisciplinary NET Medical Symposium NANETS 2025 Clinical – Chemo/SSA/Biologics (11 abstracts)
Multicenter Real-World Study of Treatment Patterns in Well-Differentiated Grade 3 (G3) Gastroenteropancreatic Neuroendocrine Tumors (GEP-NETs)
Angelo Pirozzi 1,2 , Celine Hoyek 1 , Fares Jamal 1 , Caden Collins 1 , Daniel Ahn 1 , Tanios Bekaii-Saab 1 , Timothy Hobday 4 , Patrick W McGarrah 4 , Jason Starr 3 , Thorvardur Halfdanarson 4 & Sonbol Mohamad Bassam 1
1Division of Hematology and Medical Oncology, Mayo Clinic, Phoenix, AZ, USA; 2Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy; 3Division of Hematology and Medical Oncology, Mayo Clinic, Jacksonville, FL, USA; 4Department of Oncology, Mayo Clinic, Rochester, MN, USA
Background: The 2017 WHO classification established well-differentiated G3 NETs as a distinct pathologic entity. However, their rarity and heterogeneity have hindered the definition of standard treatment strategies. Hereby, we present a multicenter real-world experience from the Mayo Clinic to inform clinical practice.
Methods: Clinical data were collected across the three Mayo Clinic sites (Minnesota, Arizona, and Florida) including patients (pts) with histologically confirmed GEP-NETs G3 between 2017and 2025. Primary endpoints included ORR, DCR, PFS, and OS. Prognostic factors were analyzed with a multivariate Cox regression.
Results: 76 pts, median age 62 years (range, 23–83), with either ab inizio (88%) or transformed (12%) G3 GEP-NETs.The most common primary sites were pancreas (60%), small bowel (17%) and rectum (5%). The median Ki-67 was 35% (range, 20–90). Most cases were non-functional (70%). Among functional tumors, carcinoid syndrome and hypoglycemia were the most common presentations (each 11.8%). Overall, median plasma 5-HIAA level was 35.5 ng/mL (range, 5–1394). 85% had de novo metastatic disease and 18% recurrent disease. Metastatic sites included liver (91%), lymph nodes (32%), bone (22%), lung and peritoneum (each 8%). The median number of metastatic sites was 1 (range, 0–5). The median number of systemic lines was 2 (range, 0–8). Across all lines, the most frequent treatments were CAPTEM (23%), PRRT with lutetium-177 DOTATATE (14%), lanreotide (11%), octreotide (8%), carboplatin-etoposide (7%), sunitinib (5%), and everolimus (5%). Efficacy outcomes were reported in Table 1 for the three most common regimens based on radiology reports. At a median follow-up of 26.4 months, mOS of the overall population was 56.2 months (95% CI, 42.9–69.5). Insulin-producing tumors (HR 6.07, 95% CI 1.33–27.5; P = 0.02) and ≥2 metastatic sites (HR 3.53, 95% CI 1.55–8.05; P = 0.003) were independently associated with poor survival.
| CAPTEM | PRRT Lu-177 | Lanreotide | ||
| Line of therapy, n (%) | ||||
| First | 24 (61.5) | 3 (12.5) | 11 (57.9) | |
| Second | 7 (17.9) | 9 (37.5) | 8 (42.1) | |
| Third or further | 8 (20.6) | 12 (50.1) | 0 (0) | |
| DCR | 62.9 | 94.7 | 50 | |
| ORR | 37.1 | 57.9 | 11.1 | |
| mPFS, months (95% CI) | 6.7 (1.8-11.5) | 11.2 (0-27.0) | 3.4 (2.0-4.2) | |
| mOS, months (95% CI) | 50.6 (15.5-85.7) | 76.1 (8.2-143.9) | NR | |
| Pooled efficacy outcomes across treatment lines. | ||||
Conclusions: Our experience underscores the use of CAPTEM and PRRT as preferred treatment choices in well-differentiated G3 GEP-NETs. Insulin secretion and metastatic burden were identified as independent predictors of poor prognosis.
Abstract ID #33418
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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