Combinations of Bevacizumab With Immune Checkpoint Inhibitors in Renal Cell Carcinoma

Cancer J. 2018 Jul/Aug;24(4):171-179. doi: 10.1097/PPO.0000000000000323.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Angiogenesis Inhibitors / administration & dosage
  • Antineoplastic Agents, Immunological / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Bevacizumab / administration & dosage
  • Biomarkers, Tumor
  • Carcinoma, Renal Cell / drug therapy*
  • Carcinoma, Renal Cell / immunology
  • Carcinoma, Renal Cell / pathology
  • Chemotherapy, Adjuvant
  • Clinical Trials as Topic
  • Humans
  • Immunomodulation / drug effects
  • Kidney Neoplasms / drug therapy*
  • Kidney Neoplasms / immunology
  • Kidney Neoplasms / pathology
  • Molecular Targeted Therapy
  • Neoadjuvant Therapy
  • Neoplasm Staging
  • Retreatment
  • Treatment Outcome

Substances

  • Angiogenesis Inhibitors
  • Antineoplastic Agents, Immunological
  • Biomarkers, Tumor
  • Bevacizumab