Effect of Atezolizumab plus Bevacizumab in Patients with Hepatocellular Carcinoma Harboring <i>CTNNB1</i> Mutation in Early Clinical Experience

Abstract

Atezolizumab plus bevacizumab (ATZ/BV) treatment is a combined immunotherapy consisting of immune checkpoint inhibitor (ICI) and anti-vascular endothelial growth factor monoclonal antibody, which has brought a major paradigm shift in the treatment of unresectable hepatocellular carcinoma (HCC). Gain-of-function mutation of <i>CTNNB1</i> contributes to resistance of ICI monotherapy through the framework of non-T-cell-inflamed tumor microenvironment. However, whether <i>CTNNB1</i> mutation renders resistance to ATZ/BV similar to ICI monotherapy remains to be elucidated. In this study, a liquid biopsy sample in plasma of 33 patients with HCC treated with ATZ/BV was subjected to droplet digital PCR for detecting hotspot mutations at the exon 3 of <i>CTNNB1</i> locus. A total of eight patients (24.2%) exhibited at least one <i>CTNNB1</i> mutation. The objective response rate (ORR) in patients with wild-type (WT) and mutant (MT) <i>CTNNB1</i> was 8.0% and 12.5%, respectively, and the disease control rate (DCR) was 68.0% and 87.5%, respectively. No significant difference in both ORR and DCR has been observed between the two groups. The median progression-free survival in patients with WT and MT <i>CTNNB1</i> was 6.6 and 7.6 months, respectively (not statistically significant). Similarly, no significant difference in overall survival has been observed between patients with WT and MT <i>CTNNB1</i> (13.6 vs. 12.3 months). In conclusion, the treatment effect of ATZ/BV in patients with HCC with MT <i>CTNNB1</i> was comparable to those patients with WT <i>CTNNB1</i>. These results implicate that BV added to ATZ might improve immunosuppressive tumor microenvironment caused by <i>CTNNB1</i> mutation.