Endocrine Abstracts

Background: GEP-NETs are increasingly diagnosed; chemotherapy remains established in high-grade, but its efficacy in low-grade is unclear.

Objectives: This study aimed to evaluate the impact of conventional chemotherapy on progression-free survival (PFS) in patients with low-grade (G1) GEP-NETs and to compare outcomes by tumour grade, primary site, and treatment regimen.

Methods: A retrospective cohort analysis was performed at St Bartholomew’s Hospital. Of 532 patients in the institutional NET database, 86 (16.2%, 95% CI: 13.0–19.3%) met inclusion criteria, defined as patients treated with first-line systemic chemotherapy between 2016–2024 who remained under active follow-up. Three patients were excluded due to incomplete or off-protocol records, leaving 83 eligible for analysis. Patients were stratified by WHO grade (G1–G3), Ki-67 index, primary site, and regimen. Among these, 18 patients (21.7%, 95% CI: 13.1–30.3%) had histologically confirmed G1 NETs (Ki-67 <3%). Kaplan–Meier curves were used to evaluate PFS.

Results: The cohort consisted of 22% G1, 31% G2, and 47% G3 NETs. Within the G1 group, 16 patients had GEP-NETs (eight pancreatic, eight gastrointestinal) and two were non-GEP (pulmonary and orbital). At baseline, 77.8% presented with metastatic disease. Median PFS in the G1 cohort was 43.7 months (95% CI: 33.1–54.3). Gastrointestinal NETs achieved the longest PFS (42.0 months), followed by pancreatic NETs (26.0 months), while non-GEP NETs had the poorest outcomes (3.4 months). Capecitabine/temozolomide (CAPTEM) demonstrated numerically superior PFS (~40 months) compared to other regimens (~20 months). Across all grades, PFS decreased with higher grade: 43.7 months (G1), 31.0 months (G2), and 13.9 months (G3).

Conclusion: Conventional chemotherapy can provide durable disease control in carefully selected patients with low-grade, well-differentiated GEP-NETs, especially gastrointestinal primaries treated with CAPTEM. By contrast, non-GEP NETs exhibited aggressive behaviour despite low Ki-67 indices. These findings align with published evidence, including trials such as E2211, which demonstrated CAPTEM activity in pancreatic NETs with median PFS of ~23 months, and retrospective series reporting PFS of 12–21 months across NET subtypes. Our observation of prolonged PFS in G1 tumours, particularly gastrointestinal primaries, suggests chemotherapy may have an under-recognised role in this setting. Further prospective evaluation is warranted.