Proton Beam Therapy Boosts Outcomes of Atezolizumab/Bevacizumab in Advanced Hepatocellular Carcinoma: A Propensity Score Analysis

Introduction Hepatocellular carcinoma (HCC) is a major cause of cancer‐related mortality, particularly in patients with advanced stage. Atezolizumab plus bevacizumab (Ate/Bev) is the standard first‐line therapy; however, its efficacy may be further enhanced using combination strategies. Methods This study evaluated the clinical impact of proton beam therapy (PBT) with Ate/Bev in patients with unresectable HCC (uHCC). We retrospectively evaluated 362 patients with uHCC treated with Ate/Bev between November 2020 and June 2023 at two centers in Taiwan. The patients were divided into the Ate/Bev‐PBT and Ate/Bev groups based on whether they received first‐line Ate/Bev combined with PBT or Ate/Bev alone. Propensity score matching was performed at a 1:2 ratio to reduce selection bias. Results There were 39 and 71 patients in the Ate/Bev‐PBT and Ate/Bev groups, respectively. Treatment‐related adverse events were comparable between the two groups and were manageable, primarily involving mild‐to‐moderate liver inflammation. Compared with the Ate/Bev group, the Ate/Bev‐PBT group demonstrated significantly better objective response rates (56.8% vs 17.3%, p < 0.001), disease control rates (75.7% vs 44.2%, p < 0.001), progression‐free survival (7.3 vs 2.3 months, p < 0.001), and overall survival (16.7 vs 7.1 months, p = 0.02). In the multivariate analysis, Ate/Bev‐PBT was strongly associated with reduced mortality (hazard ratio [HR], 0.406; 95% confidence interval [CI]: 0.236–0.700, p = 0.001) after adjusting for preserved liver function, prognostic nutritional index and receiving sequential therapy. Conclusion The addition of PBT to Ate/Bev was associated with improved treatment response and survival in patients with uHCC without compromising safety of the treatment. This combined approach may represent a promising therapeutic strategy that warrants prospective validation.