Discordant Antitumor Efficacy with Compromised Survival in High-Risk Unresectable Hepatocellular Carcinoma

Real-world data in high-risk patients remain limited; this study evaluated survival, safety, and prognostic factors in this patient group.

This multicenter study retrospectively reviewed 783 patients who received Ate/Bev from 2022-2024 across South Korea. High-risk patients (n = 252, 32.2%) were defined by main portal vein tumor thrombus (Vp4), tumor occupancy ≥50% of liver volume, or bile duct invasion. Propensity score matching (PSM) was performed to balance host-related factors between the high-risk and non-high-risk (n = 531) groups.

After PSM (251 pairs, n = 502), overall survival (median 10.4 vs. 14.9 months; HR 1.57, 95% CI 1.28-1.92, p < 0.001) and progression-free survival (median 6.0 vs. 6.8 months; HR 1.29, 95% CI 1.08-1.53, p = 0.009) remained significantly worse in the high-risk group. Objective response (25.1% vs. 19.9%, p = 0.200) and disease control rates (71.7% vs. 76.5%, p = 0.262) were comparable. Among 103 responders with documented response-onset dates, an exploratory complete-case analysis showed a numerically shorter duration of response in the high-risk group, although the difference did not reach statistical significance (median, 7.1 vs. 11.3 months; HR, 1.57; 95% CI, 0.97-2.55; p = 0.065).

Ate/Bev achieved similar antitumor response rates in high-risk and non-high-risk patients, but survival remained poorer in the high-risk group. High-risk status therefore did not preclude antitumor activity with Ate/Bev.