The current landscape for advanced hepatocellular carcinoma(HCC)has evolved drastically in recent years,with the ever-increasing development of novel standard first-line therapeutic strategies(e.g.,the combination of ...The current landscape for advanced hepatocellular carcinoma(HCC)has evolved drastically in recent years,with the ever-increasing development of novel standard first-line therapeutic strategies(e.g.,the combination of atezolizumab and bevacizumab)and the approval of several new agents for second line strategies,such as regorafenib and cabozantinib(1,2).Although a large number of treatment options are available for advanced HCC patients,multikinase inhibitor(MKI)-based immunotherapy doublet has become notably complex,especially after the publication of the COSMIC-312 trial(3).This study evaluated the efficacy and safety of cabozantinib combined with atezolizumab versus sorafenib as the first-line treatment of patients with advanced HCC.Although the primary endpoint of progression-free survival(PFS)was significantly improved with treatment using cabozantinib combined with atezolizumab compared with sorafenib in the COSMIC-312 trial,the overall survival(OS)did not improve,and the response rate was lower than expected(3).Nevertheless,this was a crucial randomized controlled trial(RCT)evaluating the efficacy of MKI-based immunotherapy doublet as the first-line systemic therapy for advanced HCC,paving the way for future investigations to determine the underlying mechanism of these connections.We have several concerns with the interpretation of this study.展开更多
文摘The current landscape for advanced hepatocellular carcinoma(HCC)has evolved drastically in recent years,with the ever-increasing development of novel standard first-line therapeutic strategies(e.g.,the combination of atezolizumab and bevacizumab)and the approval of several new agents for second line strategies,such as regorafenib and cabozantinib(1,2).Although a large number of treatment options are available for advanced HCC patients,multikinase inhibitor(MKI)-based immunotherapy doublet has become notably complex,especially after the publication of the COSMIC-312 trial(3).This study evaluated the efficacy and safety of cabozantinib combined with atezolizumab versus sorafenib as the first-line treatment of patients with advanced HCC.Although the primary endpoint of progression-free survival(PFS)was significantly improved with treatment using cabozantinib combined with atezolizumab compared with sorafenib in the COSMIC-312 trial,the overall survival(OS)did not improve,and the response rate was lower than expected(3).Nevertheless,this was a crucial randomized controlled trial(RCT)evaluating the efficacy of MKI-based immunotherapy doublet as the first-line systemic therapy for advanced HCC,paving the way for future investigations to determine the underlying mechanism of these connections.We have several concerns with the interpretation of this study.