Renal cell carcinoma (RCC) is characterized by aberrant angiogenic signaling and an immunogenic tumor microenvironment. Systemic therapies targeting vascular endothelial growth factor and the immune checkpoints programmed cell death protein 1/programmed cell death protein 1 ligand and cytotoxic T-lymphocyte-associated protein 4 have advanced to the forefront of the treatment repertoire against advanced or metastatic RCC (mRCC). In preclinical models, inhibition of vascular endothelial growth factor signaling promotes antitumor immunity and may enhance the efficacy of immune checkpoint blockade. Bevacizumab, which has previously shown antitumor activity in mRCC as monotherapy and in combination with interferon α, is now under investigation in clinical trials in combinations involving multiple immune checkpoint inhibitors. The combination of bevacizumab plus atezolizumab has demonstrated efficacy in a randomized phase III study of treatment-naive mRCC patients whose tumors express programmed cell death protein 1 ligand. We review here the preclinical rationale for combining antiangiogenic therapies with immune checkpoint inhibitors and highlight the status of current clinical development of combinations involving bevacizumab and immune checkpoint inhibitors in RCC.
Cancer journal (Sudbury, Mass.). 0000 Jan [Epub]
Xin Gao, David F McDermott