Efficacy of somatostatin analogues versus other systemic therapies as first-line palliative treatment for patients with advanced, grade 2, well-differentiated neuroendocrine tumours of extra-pulmonary origin with a Ki-67 index between 10% and 20%

Eleni Vrana; Klaire Exarchou; Amina Dawoodji; Cong Zhou; Christina Nuttall; Manyi Eyong; Kelly Farrell; Natalie Barratt; Sarah McConnell; Katie Dennison; Nadina Tinsley; Alicia-Marie Conway; Hubner Richard A.; McNamara Mairead G.; Moore Andrew R.; Pritchard D. Mark; Frizziero Dr Melissa

doi:10.1530/endoabs.114.OC4

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Endocrine Abstracts (2025) 114 OC4 | DOI: 10.1530/endoabs.114.OC4

UKINETS2025 23rd National Conference of the UK and Ireland Neuroendocrine Tumour Society 2025 Oral Communications (4 abstracts)

Efficacy of somatostatin analogues versus other systemic therapies as first-line palliative treatment for patients with advanced, grade 2, well-differentiated neuroendocrine tumours of extra-pulmonary origin with a Ki-67 index between 10% and 20%

Eleni Vrana ¹ , Klaire Exarchou ² , Amina Dawoodji ¹ , Cong Zhou ³ , Christina Nuttall ¹ , Manyi Eyong ¹ , Kelly Farrell ¹ , Natalie Barratt ¹ , Sarah McConnell ¹ , Katie Dennison ¹ , Nadina Tinsley ¹ , Alicia-Marie Conway ^1,4 , Richard A. Hubner ¹ , Mairéad G. McNamara ^4,1 , Andrew R. Moore ⁵ , D. Mark Pritchard ^5,6 & Dr Melissa Frizziero ¹

Author affiliations

¹Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester, United Kingdom; ²Department of Upper GI Surgery, University Hospitals of Liverpool Group, Liverpool, United Kingdom; ³Bioinformatics and Biostatistics, Cancer Research UK National Biomarker Centre, Manchester, United Kingdom; ⁴Division of Cancer Sciences, University of Manchester, Manchester, United Kingdom; ⁵Department of Gastroenterology, University Hospitals of Liverpool Group, Liverpool, United Kingdom; ⁶Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, United Kingdom

Background: In patients with advanced, grade 2 (G2), well-differentiated neuroendocrine tumours (WD-NETs) with Ki-67 ≥10% and ≤20% (“G2 high”), chemotherapy or protein kinase inhibitors (PKIs) are recommended options in the first-line palliative setting. Somatostatin analogue (SSA) therapy is a well tolerated alternative, yet randomised evidence is lacking.

Methods & Aims: A retrospective study was conducted in patients with locally advanced or metastatic “G2 high” WD-NETs of extra-pulmonary origin, diagnosed between 01/01/2009-31/02/2024, and treated at two European Neuroendocrine Tumour Society (ENETS) Centres of Excellence. Eligible patients had ≥1 line of palliative systemic treatment and were followed up for ≥6 months. The aim was to compare progression free survival (PFS) and overall survival (OS) of first-line SSA versus (vs) other systemic therapies (non-SSA). Chi-square test, Kaplan-Meier and Cox-regression analysis were applied as appropriate.

Results: Seventy-eight patients were identified. Clinical-pathological characteristics at start of first-line; male 54%, median age 61.7 years, pancreas 45%, small bowel 39%, other sites of origin 16%, distant metastases 86%, ECOG performance status 0-1 90%, median Ki-67 14%, functioning tumour 28%. First-line choice; SSA 68%, chemotherapy 24%, PKIs 8%. SSA/non-SSA combinations were not applied for functioning tumours. First-line discontinuation due to toxicity; SSA 0% vs non-SSA 24% (P < 0.001). Median age was higher in the SSA arm (64.4 vs 57.5 years, P = 0.029). Median Ki-67 did not differ between the two arms (13% vs 15%, P = 0.094). Presence of distant metastases; SSA 85% vs non-SSA 88% (P = 0.770); liver metastases 81% vs 84% (P = 0.821). Non-SSA was preferred for pancreatic primaries (57% vs 43%, P < 0.001); SSA for small bowel primaries (90% vs 10%, P < 0.001) or functioning tumours (91% vs 9%, P < 0.001). Median PFS for SSA vs non-SSA; 10.8 vs 15.9 months (HR=1.08, 95%CI 0.63-1.84, P = 0.788). Median OS; 35.1 vs 30.2 months (HR=0.62, 95%CI 0.33-1.15, P = 0.129). No clinical-pathological characteristic impacted PFS or OS.

Conclusions: In this study, SSA was a similarly effective first-line option to non-SSA for patients with advanced “G2 high” WD-NETs. Data from larger prospective studies are required for validation and to more reliably interrogate impact of clinical-pathological variables and further treatment lines.