Efficacy of surufatinib in advanced Grade 3 neuroendocrine tumors: a real-world, national, multicenter study

Background: Well-differentiated Grade 3 neuroendocrine tumors (G3 NETs) represent a heterogeneous entity with limited therapeutic standards. Surufatinib, a small-molecule inhibitor, has shown efficacy in G1/G2 NETs, but its specific role in the G3 subpopulation and optimal patient selection strategies remain to be elucidated. Objectives: This study aimed to evaluate the real-world efficacy of surufatinib in G3 NETs and identify the factors that influenced progression-free survival (PFS). Design: A national, multicenter, retrospective observational study. Methods: We analyzed data from 77 patients with unresectable or metastatic G3 NETs (Ki-67 > 20%) treated with surufatinib across 15 centers in China between January 2021 and April 2024. The reporting of this study conforms to the STROBE statement. The primary endpoint was PFS. A multivariable Cox proportional hazards model was used to explore prognostic factors. Results: The median Ki-67 index was 30% (range: 22%−70%), and 49 patients were of pancreatic origin. A total of 11 patients were treatment-naïve, and 27 patients received surufatinib-based combination therapy. The overall median PFS was 9.4 months (95% confidence interval: 8.5–13.0), and the objective response rate (ORR) was 22.1%. Patients with a Ki-67 index ⩽ 30% had longer PFS than the Ki-67 > 30% group (12.6 vs 9.0 months, hazard ratio = 0.270, p = 0.003). Combined treatment showed a numerical trend toward improved ORR (33.3% vs 16.0%, p = 0.08), but did not significantly prolong PFS compared to surufatinib monotherapy (9.7 vs 9.4 months, p = 0.64). Conclusion: Surufatinib was a promising therapeutic option for G3 NETs. Prospective, larger-scale cohorts are warranted to confirm the efficacy and address the predictive markers for better patient selection.