Abstract
Neuroendocrine carcinoma (NEC), neuroendocrine tumor grade 3 (NET G3), and pancreatic cancer (PC) are aggressive malignancies with limited effective treatments. This study assessed the efficacy and safety of surufatinib combined with the PD-1 inhibitor sintilimab, with or without chemotherapy. In this phase II trial, 51 patients with advanced NEC (n = 30), NET G3 (n = 12), or PC (n = 9) received surufatinib plus sintilimab; the NEC cohort additionally received chemotherapy. The primary endpoint was progression-free survival (PFS). Secondary endpoints included objective response rate (ORR), disease control rate (DCR), overall survival (OS), and safety. As of August 31, 2025, the median follow-up was 18.6 months. In the NEC cohort, median PFS was 7.3 months, median OS was 13.3 months, and ORR was 53.3%. First-line NEC patients achieved superior outcomes (mPFS 7.6 months; mOS 14.3 months; ORR 65.0%) versus later-line therapy. Median PFS was 6.8 months in the NET G3 cohort and 2.1 months in the PC cohort. Adverse events were manageable; no treatment-related death occurred. Surufatinib plus sintilimab with or without chemotherapy shows encouraging efficacy and acceptable safety in advanced NEC, NET G3, and PC. This clinical trial was registered at ClinicalTrials.gov (NCT05627427) on November 15, 2022.
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Acknowledgements
We sincerely thank all patients and their families for their participation and support in this study. We also acknowledge the contributions of the clinical staff and pathologists from the Department of Pathology and the Department of Hepatobiliary and Pancreatic Surgery for sample collection and technical assistance. This work was supported by Tianjin Science and Technology Commission key project (25JCLZJC00360), Special Research Fund for Clinical Studies of Innovative Drugs after Market Launch (WKZX2024CX102217), Wu Jieping Medical Foundation Special Fund for Clinical Research (320.6750.2024-10-1), CACA Regional Scientific Research Cultivation Fund in Oncology Field (CESTDQLCORP300-04) and Tianjin Key Medical Discipline Construction Project (TJYXZDXK-3-003A). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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Ji, Z., Wang, X., Ma, L. et al. Efficacy and safety of surufatinib and sintilimab with or without chemotherapy for advanced high-grade neuroendocrine neoplasms and pancreatic cancer. npj Precis. Onc. (2026). https://doi.org/10.1038/s41698-026-01478-y
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DOI: https://doi.org/10.1038/s41698-026-01478-y
