Atezolizumab and Bevacizumab With Photon Radiotherapy for Unresectable Hepatocellular Carcinoma

Progression free survival (PFS)

Atezolizumab (anti-programmed death-ligand 1; anti-PD-L1) in conjunction with bevacizumab
 (anti-vascular endothelial growth factor; anti-VEGF) has become the established standard
 first-line systemic treatment for unresectable hepatocellular carcinoma (HCC). Despite an
 improved objective response rate (ORR) of 27%, the majority of patients face HCC progression
 and liver failure [Finn et al., N Engl J Med 2020]. Developing a new combined treatment
 strategy to overcome resistance to anti-PD-L1 and anti-VEGF is essential to improve patient
 outcomes.
 
 Radiation treatment (RT) is highly efficacious in controlling localized solid tumors and has
 become an integral component of the treatment algorithm for unresectable HCC. Importantly, a
 recent retrospective cohort described that RT combined with atezolizumab plus bevacizumab was
 associated with favorable median overall survival of 16.1 months (Manzar et al, Cancers
 2022). Our preclinical study (Hsieh et al., Science Immunology 2022) revealed that RT
 combined with PD-L1/PD-1 blockade induces immunogenic cell death and tumor antigen
 cross-presentation in antigen-presenting cells, thereby potentiating the systemic antitumor T
 cell responses in murine tumor models. However, whether the combinatorial therapy with RT,
 atezolizumab, and bevacizumab can trigger synergistic antitumor effects and systemic immune
 mobilization has not yet been validated in clinical trials for unresectable HCC.
 
 Both atezolizumab/bevacizumab and X-ray RT are approved treatment methods for unresectable
 HCC by the U.S. and Taiwan Food and Drug Administration (FDA). The present phase II
 non-randomized trial aims to prospectively document the therapeutic efficacy, safety, and
 immunological responses in patients with unresectable HCC treated with
 atezolizumab/bevacizumab combined with conventional photon radiotherapy.