Adjuvant Sintilimab with or without Anti-VEGF Therapy After Resection in Hepatocellular Carcinoma with Microvascular...

Patients with hepatocellular carcinoma (HCC) and microvascular invasion (MVI) face high post-resection relapse risk. Whether adjuvant PD-1 alone or with anti-vascular endothelial growth factor (anti-VEGF) improves outcomes remains uncertain.

Between 1 January 2022 and 1 January 2023, 170 consecutive patients from three Chinese centers were retrospectively reviewed. After resection, 69 received observation, 46 received intravenous sintilimab, and 55 received sintilimab plus either oral lenvatinib or intravenous bevacizumab biosimilar. Recurrence-free survival (RFS) was analyzed with Kaplan-Meier estimates and Cox models.

Median follow-up was 24.7 months. Recurrence or death occurred in 42/69 (60.9%) observation patients, 19/46 (41.3%) sintilimab patients, and 23/55 (41.8%) combination patients. Median RFS was 16.1 months after observation, versus 29.5 months with sintilimab (hazard ratio=0.55, 95% confidence interval=0.32-0.95; P = 0.033) and 30.5 months with sintilimab plus anti-VEGF therapy (hazard ratio=0.55, 95% confidence interval=0.33-0.92; P = 0.023). One- and two-year RFS rates were 58.0% and 40.0% for observation, 73.9% and 66.6% for sintilimab, and 81.8% and 63.0% for combination therapy. Overall survival analysis is immature, median overall survival has not been reached in any group.

Adjuvant sintilimab, with or without anti-VEGF therapy, significantly prolonged RFS compared with surgery alone in patients with MVI-positive HCC. The magnitude of benefit was comparable between monotherapy and combination therapy, indicating that routine addition of anti-VEGF therapy may not be necessary for all patients.