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

内容摘要

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. This study aimed to evaluate the real-world efficacy of surufatinib in G3 NETs and identify the factors that influenced progression-free survival (PFS). A national, multicenter, retrospective observational study. 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. 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). 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. Could surufatinib benefit patients with Grade 3 neuroendocrine tumor? What was studied: Grade 3 neuroendocrine tumor (G3 NET) is a rare, well-differentiated, but aggressive type of cancer with limited treatment options. Surufatinib is a targeted therapy that blocks the growth of blood vessels that feed tumors. While it has been already approved in China for patients with G1 and G2 neuroendocrine tumors, it is unclear whether G3 NET patients could also benefit, and if so, what factors influence how long patients can live on surufatinib before their cancer progresses. What we did: We analyzed data from 77 patients with G3 NET who were treated with surufatinib from 15 hospitals across China between 2021 and 2024. What we found: About 22% of patients saw their tumors shrink (more than 30%). On average, patients went 9.4 months without their cancer getting worse. Patients with lower Ki-67 levels (30% or below), which is a marker of how quickly tumor cells grow, lived a median of 12.6 months without progression compared to 9.0 months for those with higher Ki-67 levels. In addition, combining surufatinib with other treatments led to more tumor shrinkage, but did not significantly extend the time before the cancer started growing again. What did these results mean: Surufatinib is a promising therapeutic option for G3 NET patients. We need larger studies to confirm how well surufatinib works and figure out which patients benefit the most.