There is preclinical and clinical data on synergistic activity of angiogenesis inhibitors and anti-programmed death-1 (anti-PD-1) targeted therapy. Targeting VEGFR decreased T-regulatory cells and Myeloid-derived suppressor Cells. In addition, VEGF-A produced in the tumor microenvironment enhanced expression of PD-1 involved in CD8 T cell exhaustion8. The combination of targeted therapy and immune-checkpoint inhibitors (ICIs), either in a parallel or sequential manner, could theoretically lead to enhanced anti-tumor responses, reflected in durable responses and prolonged survival. However, there have been lack of clinical data of targeted agents who developed progressive disease with ICIs.~In previous phase I study, pharmacodynamics indicated a sustained occupancy of > 70% of PD-1 molecules on circulating T-cells ≥ 2 months following infusion. Based on these findings, ICI use may retain the prolonged effect even after discontinuation. There was a case report of a sorafenib-refractory patient experiencing progressive disease during ICI combination treatment with the anti-PD-1 antibody and the anti-GITR antibody within phase I trial followed by a prolonged tumor response during third-line regorafenib monotherapy.~In patients with advanced HCC, anti-VEGF monoclonal antibodies, multi-kinase inhibitor (sorafenib, regorafenib, cabozantinib and lenvatinib) and ICIs are available treatment options, however, treatment sequencing and combination strategy are challenging.~Atezolizumab plus bevacizumab demonstrated survival benefit and established as a new first-line therapy, hence it is clinically important to study the efficacy and toxicity of regorafenib after treatment with ICIs or ICI combination.
To investigate efficacy and toxicity of regorafenib after treatment with atezolizumab and bevacizumab combination