Evaluating the Safety and Efficacy of Adding Liver-Directed Radiation Therapy to Atezolizumab and Bevacizumab in Advanced Hepatocellular Carcinoma

OBJECTIVES: Radiation therapy (RT) may potentiate an antitumor immune response when combined with immunotherapy in advanced hepatocellular carcinoma (HCC) but carries the potential risk of bowel toxicity and impaired liver function. We describe our single-center experience of adding liver-directed RT to atezolizumab and bevacizumab (A/B) in patients with advanced HCC. METHODS: This was a single-center retrospective cohort study of patients with HCC naive to systemic therapy who received A/B with or without liver-directed RT from January 1, 2020 until May 1, 2023. We assessed safety outcomes, the real-world response rate (rwRR), overall survival (OS), and time-to-progression (TTP) from initiation of A/B. Time-to-event outcomes were analyzed by Kaplan-Meier methodology. Given anticipated baseline imbalances between cohorts, no formal comparisons were performed. RESULTS: We identified 49 patients (n=34 control, n=15 RT) who met the inclusion criteria. The cohorts differed in the presence of ascites, baseline liver dysfunction, infection with hepatitis B, and alcoholic liver disease. Two patients in the control group (5.8%) and 1 patient in the RT group (6.7%) experienced clinically significant bleeding. One patient (6.7%) developed possible RT-induced liver disease. The rwRR in the RT group was 73.3% (11/15) compared with 17.6% (6/34) in the control group. The median OS in the RT group was 14.4 months, and 10.8 months in the control group. Median TTP was 6.4 months with RT compared with 5.8 months in the control group. CONCLUSIONS: The addition of liver RT to A/B resulted in limited additional toxicity with increased response rates, although significant differences in baseline characteristics limit a full interpretation of this data. Ongoing trials and trials under development will provide informative data regarding the addition of RT to A/B, particularly to assess the impact on OS and TTP.