Atezolizumab plus Bevacizumab — A Landmark in Liver Cancer
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More than a decade ago, sorafenib became the first systemic therapy that conferred a meaningful survival benefit in the treatment of advanced hepatocellular carcinoma. Since then, no treatment had surpassed the effect of sorafenib in the first line until the regimen of atezolizumab and bevacizumab now reported.

Treatment with the combination of atezolizumab, a programmed death ligand 1 (PD-L1) inhibitor, and bevacizumab, a monoclonal antibody targeting the vascular endothelial growth factor, resulted in significantly longer overall and progression-free survival as well as strikingly better patient- reported outcomes than sorafenib.

These data are momentous, since they identify not only the first therapy to improve survival beyond sorafenib, but also the first successful combination regimen and the first positive randomized, phase 3 trial of immune checkpoint inhibition in this challenging cancer. In defining the new role of atezolizumab–bevacizumab in the expanding treatment landscape for hepatocellular carcinoma, several aspects of the trial data warrant further scrutiny, including the extent of bleeding risk and implications for a broader population.

In addition, subgroup analyses should be performed to discern candidate biomarkers in the context of other immune checkpoint inhibitor trials, and outcomes should be examined for signals of synergy as opposed to additive efficacy, a question that could inform decisions about whether to use a combination or a sequential strategy.