Treatment outcomes and survival in advanced gastroenteropancreatic neuroendocrine carcinoma

Introduction: Gastroenteropancreatic neuroendocrine carcinomas (GEP-NECs) are aggressive malignancies with limited therapeutic options. Real-world data are needed to evaluate treatment outcomes. Materials and methods: We conducted a retrospective cohort study of patients with histologically confirmed, unresectable locally advanced or metastatic GEP-NEC treated at a United Kingdom (UK) tertiary referral centre between 2015 and 2025. Clinical characteristics and outcomes were extracted from electronic records. Survival outcomes were estimated using Kaplan–Meier methods. Prognostic factors were analysed using Cox proportional hazards models. Results: In total, 80 patients with advanced GEP-NEC comprised the overall cohort, of whom 57 received first-line systemic therapy and were included in the treatment outcome analysis. The median age of the treated cohort was 65 years, and 61% were male. Most patients presented with metastatic disease (79%), commonly involving the liver (54%). Carboplatin–etoposide was the predominant first-line regimen (88%). The objective response rate (ORR) was 54%, and the disease control rate (DCR) was 74%. Median real-world progression-free survival (rwPFS) was 6.5 months (95% confidence interval (CI) 5.3–7.7), and median overall survival (OS) was 13.7 months (95% CI 10.1–17.2). In the multivariate analysis, Eastern Cooperative Oncology Group (ECOG) performance status ≥2 (hazard ratio (HR) 2.99, p = 0.030) and largest liver metastasis ≥2 cm (HR 2.08, p = 0.038) were independently associated with worse survival. Second-line therapies demonstrated limited activity, with a median rwPFS of 2.5 months. Molecular profiling identified actionable alterations in a small subset of patients. Conclusions: Platinum–etoposide remains the most active first-line treatment for advanced GEP-NEC, but outcomes remain modest. Exploratory analysis identified poor performance status and largest liver metastasis ≥2 cm as factors associated with inferior survival. Subsequent therapies provide limited benefit, underscoring the need for more effective treatment strategies and the potential value of molecular profiling.