First-line immune checkpoint inhibitor-based combinations in unresectable hepatocellular carcinoma: current management and future challenges.

Introduction Immunotherapy has recently taken on an extremely important role in medical oncology, as first- or later-line treatment in several tumor types, and recent years have seen the emerging of clinical trials assessing immune checkpoint inhibitors (ICIs) in unresectable hepatocellular carcinoma (HCC). Areas covered Herein, we provide an overview of recently published studies exploring the dual immune checkpoint blockade or the combination of ICIs plus biological treatments as first-line treatment in HCC patients with advanced disease, especially focusing on the biological rationale behind these therapeutic strategies, and ongoing active and recruiting clinical trials. Expert opinion Results of studies on monotherapy with ICIs have suggested that this strategy could be beneficial only in a minority of patients; conversely, the recently published IMbrave150 study has reported an overall survival benefit in HCC receiving the combination of atezolizumab plus bevacizumab compared to sorafenib as first-line treatment. A wide number of clinical trials is evaluating ICI-based combinations in advanced HCC, a strategy which is supported by robust preclinical and early-phase clinical data, and results of these studies are highly awaited.