Evaluation of hyperprogressive disease with atezolizumab plus bevacizumab for hepatocellular carcinoma: A secondary analysis of the <scp>IMbrave150</scp> trial

The use of Immune checkpoint inhibitors (ICIs) as monotherapy for patients with hepatocellular carcinoma (HCC) has been associated with an increased risk of hyperprogressive disease (HPD), the occurrence of which carries a poor prognosis. However, it is unknown whether contemporary frontline treatment with the combination of atezolizumab and bevacizumab causes significant HPD. This study conducted a secondary analysis of patient-level data from the IMbrave150 randomized controlled trial of atezolizumab plus bevacizumab versus sorafenib for frontline treatment of HCC. Multiple established definitions of early progression and treatment failure applicable to clinical trials were evaluated, including Response Evaluation Criteria in Solid Tumours (RECIST) HPD, HPD based on percent change of sum of longest diameter (SLD HPD), treatment failure HPD (TF HPD), and fast progression (FP). The incidence of these measures was compared between arms. The risk factors for and prognosis of TF HPD were evaluated. The risk of RECIST HPD and TF HPD was significantly lower with atezolizumab plus bevacizumab treatment than with sorafenib treatment-odds ratio for RECIST HPD: 0.29 (95% CI 0.01 to 0.82), TF HPD: 0.30 (0.17, 0.54). TF HPD was similarly associated with poor prognosis, irrespective of treatment arm. High blood alpha-fetoprotein and neutrophil-to-lymphocyte ratio were both associated with an increased risk of TF HPD. For all definitions of early progression/treatment failure, the risk was either significantly lower with atezolizumab plus bevacizumab than with sorafenib, or there were no differences. Atezolizumab plus bevacizumab treatment is unlikely to cause significant HPD.