Factors associated with immunotherapy response for hepatocellular carcinoma.
Authors: Matthew Shing Hin Chung, Rex Wan-Hin Hui, Lu Li, Xianhua Mao, Chi Leung Chiang, Carlos K. H. Wong, Ian Chi Kei Wong, Man Fung Yuen, Wai-Kay Seto, Lung-Yi Mak
Journal: Journal of Clinical Oncology (2025)

4106 Background: Immunotherapy has shown remarkable progress in treating hepatocellular carcinoma (HCC) in recent years. We aim to investigate the clinical factors associated with treatment response to HCC immunotherapy in Asian population. Methods: We identifiedHCC patients receiving immunotherapy (nivolumab, pembrolizumab, atezolizumab, durvalumab, tremelimumab, ipilimumab; including monotherapies or combinations) from January 2008 to June 2024 from a population-based cohort in Hong Kong. Primary outcomes were all-cause mortality and hospitalization stratified by etiology of HCC [Viral-HCC, defined as hepatitis B virus (HBV)-related or/and hepatitis C virus (HCV)-related HCC vs non-viral-HCC], other clinical factors including age, sex, type 2 diabetes (T2D), cirrhosis, antiviral therapy for HBV, and history of receiving other oncological treatment (curative: surgical resection, liver transplant, radiofrequency ablation, microwave ablation; non-curative: transcatheter arterial chemoembolization and radiotherapy). Hazard ratios (HR) were estimated by Cox regression models. Results: This study included 1363 patients on immunotherapy (mean age 63.1 years, 84.2% male; 87.2% viral-HCC; 23.0% had prior curative therapy; 34.5% had prior non-curative therapy). Over 240-days of median follow-up, viral-HCC had similar risk of all-cause mortality (54.5% vs 58.9%, p = 0.169) and hospitalization (34.8% vs 30.9%, p = 0.360) compared to non-viral-HCC. Patients with prior curative therapy compared to those without had lower risk of all-cause mortality (HR 0.81 [95% CI: 0.69-0.95], p = 0.011). Among HBV-related HCC, those with antiviral treatment ≥2 years prior to immunotherapy were associated with lower risk of liver-specific mortality (HR 0.83 [95% CI 0.70-0.99], p = 0.036) and HCC-specific mortality (HR 0.80 [95% CI 0.67-0.96], p = 0.014). Patients with cirrhosis had higher risk of all-cause mortality (HR 1.42 [95% CI 1.18-1.71], p &lt; 0.001). No associations with treatment response were observed in subgroups stratified by age &lt; 60/ ≥60, sex, and T2D. Conclusions: Among patients with HCC receiving immunotherapy, treatment outcomes were similar in viral-etiologies and non-viral etiologies. Antiviral treatment improves treatment response in HBV-related HCC, while cirrhosis is detrimental to mortality outcomes. HCC immunotherapy following curative treatment, in contrast to non-curative therapies, has improved treatment response. All-cause mortality Hospitalization HR 95% CI P value HR 95% CI P value Viral-HCC 0.86 (0.70, 1.06) 0.169 1.14 (0.86, 1.51) 0.360 Age (&lt;60/ ≥60) 0.91 (0.79, 1.06) 0.238 0.90 (0.76, 1.08) 0.276 Sex 0.98 (0.81, 1.18) 0.812 0.99 (0.78, 1.26) 0.939 T2D 1.00 (0.86, 1.15) 0.957 0.84 (0.70, 1.02) 0.082 Cirrhosis 1.42 (1.18, 1.71) &lt;0.001 1.23 (0.99, 1.52) 0.062 Curative therapy 0.81 (0.69, 0.95) 0.011 1.09 (0.88, 1.33) 0.434 Non-curative therapy 1.11 (0.96, 1.29) 0.147 1.60 (1.34, 1.92) &lt;0.001