The impact of atezolizumab and bevacizumab in hepatocellular carcinoma with activated ß-catenin signaling.

Background To date, no biomarkers exist to predict response or resistance to immunotherapy in hepatocellular carcinoma (HCC). Recent approaches to classify HCC into different immunological states revealed a negative correlation between Wnt/s-catenin activation and immunogenicity and T-cell infiltration. If these "cold" tumors with primary resistance to checkpoint inhibition (CPI) may benefit from dual treatment of CPI and anti-angiogenic therapy has not been proved. Case Here, we describe the case of a male patient with metastatic HCC. After failure of standard of care treatment with lenvatinib, sorafenib and ramucirumab fourth-line systemic therapy with atezolizumab and bevacizumab were applied leading to a phenomenal response. Immunohistochemical evaluations were compatible with Wnt/s-catenin pathway activation and accompanying low T-cell infiltration as well as low PD-L1 score. Conclusion Patients with Wnt/s-catenin activation may benefit from combination therapy with atezolizumab and bevacizumab regardless of potential predictive markers for immune checkpoint inhibition.