Preclinical evidence indicates that VEGF and VEGF-dependent angiogenesis may induce immune suppression in tumors by impairing antigen presenting cells and effector T-cells, and enhancing T-regulatory cells and monocytes. Thus, targeting VEGF may reprogram the tumor immune microenvironment to render cancers more vulnerable to immunotherapies. Indeed, the use of anti-VEGF strategies as an immunotherapy adjuvant has been associated with clinical benefit in multiple cancer types including HCC, and no new safety signals. While the clinical benefit of monotherapy axitinib in HCC is modest, use of axitinib as an immunotherapy adjuvant may circumvent primary resistance mechanisms to immune checkpoint inhibitors in HCC leading to more frequent or robust anti-tumor immunity.~Given the complimentary immune augmenting mechanisms of targeting VEGF and phosphatidylserine, combination axitinib, bavituximab, and avelumab, a PD-L1 antibody, represents a novel and rational immunotherapy regimen in HCC.
Across cancer types, immune checkpoint inhibitors have been shown to induce complete response, partial response, and stable disease after initial evidence of radiographic increase in tumor burden. Treatment beyond progression should be considered when the patient is stable (or improving) symptomatically and if tumor reassessment can be performed within a short period.