Combinations of Bevacizumab With Cancer Immunotherapy

• Published in: The cancer journal (Sudbury, Mass.) Vol. 24; no. 4; p. 193
• Main Authors: Chen, Daniel S, Hurwitz, Herbert
• Format: Journal Article
• Language: English
• Published: United States 01.07.2018
• Subjects: Angiogenesis Inhibitors - administration & dosage; Angiogenesis Inhibitors - therapeutic use; Antineoplastic Agents, Immunological - administration & dosage; Antineoplastic Agents, Immunological - therapeutic use; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; B7-H1 Antigen - antagonists & inhibitors; Bevacizumab - administration & dosage; Bevacizumab - therapeutic use; Biomarkers, Tumor; Clinical Trials as Topic; Humans; Immunomodulation - drug effects; Immunotherapy; Molecular Targeted Therapy; Neoplasms - drug therapy; Neoplasms - immunology; Neoplasms - metabolism; Neoplasms - pathology; Programmed Cell Death 1 Receptor - antagonists & inhibitors; T-Lymphocytes - drug effects; T-Lymphocytes - immunology; T-Lymphocytes - metabolism; Vascular Endothelial Growth Factor A - antagonists & inhibitors
• ISSN: 1540-336X
• DOI: 10.1097/ppo.0000000000000327

Cancer immunotherapy (CIT) has transformed cancer treatment. In particular, immunotherapies targeting the programmed death ligand 1 (PD-L1)/programmed death 1 pathway have demonstrated durable clinical benefit in some patients. However, CIT combinations may create a more favorable environment in which to maximize the potential of the immune system to eliminate cancer. Here we describe 3 key mechanisms related to vascular endothelial growth factor (VEGF)-mediated immunosuppression: inhibition of dendritic cell maturation, reduction of T-cell tumor infiltration, and promotion of inhibitory cells in the tumor microenvironment; supporting data are also described. In addition, we discuss immunomodulatory properties observed within tumors following bevacizumab treatment. Combining anti-PD-L1 and anti-VEGF therapies has shown synergy and positive outcomes in phases I to III studies, particularly in settings where high VEGF levels are known to play an important role in tumor growth. We also review data from key studies supporting combination of bevacizumab and CIT, with a focus on PD-L1/programmed death 1 inhibitors.