Adjuvant donafenib plus sintilimab therapy for hepatocellular carcinoma at high risk of recurrence after resection: a retrospective cohort study
- 1Faculty of Hepato‐Pancreato‐Biliary Surgery, The First Medical Center, Chinese People's Liberation Army (PLA) General Hospital
Abstract
Background: Hepatocellular carcinoma (HCC) carries a high recurrence risk after curative resection, yet effective adjuvant strategies remain lacking. Although donafenib plus anti-PD-1 monoclonal antibodies has shown efficacy in advanced HCC, the effectiveness in patients at high recurrence risk after curative resection remains unclear.
Methods: This retrospective cohort study included 143 patients with high-risk HCC after curative resection between June 2019 and April 2024. Patients received adjuvant donafenib plus sintilimab (n=76) or active surveillance (n=67). IPTW, stabilized IPTW (sIPTW), and propensity score matching (PSM) were applied to reduce baseline imbalance. The primary endpoint was recurrence-free survival (RFS), with overall survival (OS) and treatment-emergent adverse events (TEAEs) as secondary endpoints. Survival outcomes were assessed using Kaplan–Meier analysis and Cox regression models.
Results: After IPTW adjustment, adjuvant donafenib plus sintilimab was associated with improved RFS compared with surveillance (median RFS, 22.4 vs. 17.4 months; P = 0.036). The 12- and 24-month RFS rates were 78.2% and 44.4% versus 64.4% and 33.2%, respectively. Multivariable Cox analysis confirmed an independent association between adjuvant therapy and reduced recurrence risk (HR, 0.58; 95% CI, 0.35–0.96; P = 0.036), with consistent results in sIPTW and PSM analyses. OS showed a favorable but nonsignificant trend. Subgroup analyses demonstrated a consistent trend toward RFS benefit across most clinically relevant strata. Among treated patients, TEAEs occurred in 72.4%, mainly grade 1–2 events; grade ≥3 events occurred in 7.9%, with no treatment-related deaths.
Conclusions: Adjuvant donafenib plus sintilimab was associated with improved RFS in patients with high-risk HCC, with an acceptable safety profile, supporting its potential as a risk-adapted adjuvant strategy that warrants further validation in prospective studies.
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BibTeX
@article{li2026adjuvant,
title = {{Adjuvant donafenib plus sintilimab therapy for hepatocellular carcinoma at high risk of recurrence after resection: a retrospective cohort study}},
author = {Chenggang Li and Hanchuan Shen and Yang Liu and Tianci Zhao and Chaoxian Li},
journal = {Frontiers in Immunology},
year = {2026},
month = oct,
doi = {10.3389/fimmu.2026.1736128},
url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1736128/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Adjuvant donafenib plus sintilimab therapy for hepatocellular carcinoma at high risk of recurrence after resection: a retrospective cohort study
AU - Chenggang Li
AU - Hanchuan Shen
AU - Yang Liu
AU - Tianci Zhao
AU - Chaoxian Li
PY - 2026
DA - 2026/10/14
JO - Frontiers in Immunology
DO - 10.3389/fimmu.2026.1736128
UR - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1736128/full
AB - Background: Hepatocellular carcinoma (HCC) carries a high recurrence risk after curative resection, yet effective adjuvant strategies remain lacking. Although donafenib plus anti-PD-1 monoclonal antibodies has shown efficacy in advanced HCC, the effectiveness in patients at high recurrence risk after curative resection remains unclear. Methods: This retrospective cohort study included 143 patients with high-risk HCC after curative resection between June 2019 and April 2024. Patients received adjuvant donafenib plus sintilimab (n=76) or active surveillance (n=67). IPTW, stabilized IPTW (sIPTW), and propensity score matching (PSM) were applied to reduce baseline imbalance. The primary endpoint was recurrence-free survival (RFS), with overall survival (OS) and treatment-emergent adverse events (TEAEs) as secondary endpoints. Survival outcomes were assessed using Kaplan–Meier analysis and Cox regression models. Results: After IPTW adjustment, adjuvant donafenib plus sintilimab was associated with improved RFS compared with surveillance (median RFS, 22.4 vs. 17.4 months; P = 0.036). The 12- and 24-month RFS rates were 78.2% and 44.4% versus 64.4% and 33.2%, respectively. Multivariable Cox analysis confirmed an independent association between adjuvant therapy and reduced recurrence risk (HR, 0.58; 95% CI, 0.35–0.96; P = 0.036), with consistent results in sIPTW and PSM analyses. OS showed a favorable but nonsignificant trend. Subgroup analyses demonstrated a consistent trend toward RFS benefit across most clinically relevant strata. Among treated patients, TEAEs occurred in 72.4%, mainly grade 1–2 events; grade ≥3 events occurred in 7.9%, with no treatment-related deaths. Conclusions: Adjuvant donafenib plus sintilimab was associated with improved RFS in patients with high-risk HCC, with an acceptable safety profile, supporting its potential as a risk-adapted adjuvant strategy that warrants further validation in prospective studies.
SN - 1664-3224
ER -