Atezolizumab-bevacizumab plus Y-90 TARE for the treatment of hepatocellular carcinoma: preclinical rationale and ongoing clinical trials.

Introduction: The treatment algorithm of advanced hepatocellular carcinoma (HCC) has evolved since the introduction of immunotherapy. The IMbrave150 trial set atezolizumab-bevacizumab as a new standard-of-care first-line treatment for unresectable HCC patients. However, for patients with intermediate or advanced stage with portal vein thrombosis but without distant metastases, Yttrium transarterial radioembolization (Y-TARE) is considered the treatment of choice.

Areas Covered: We discuss the main evidence regarding the use of Y-TARE in HCC, the recent progress of immunotherapy in this tumor, and the preclinical rationale of combining VEGF blockade with the other two treatment strategies.

Expert Opinion: HCC has an extremely heterogeneous tumor immune microenvironment. This may explain the inconsistent outcomes obtained with immune-checkpoint inhibitors. The identification of patients who could benefit most from immunotherapy is crucial; however, reliable markers of response are lacking. Radiation therapy and VEGF inhibition have an established synergism with immunotherapy, mainly linked to enhanced antigen presentation and reduced immunosuppressive immune infiltrate. Combining an immune-checkpoint inhibitor with VEGF blockade and Y-TARE might hence overcome primary resistances observed when each of these treatments is administerd alone.