Anti-angiogenic agents in the age of resistance to immune checkpoint inhibitors: Do they have a role in non-oncogene-addicted non-small cell lung cancer?. (June 2020)

• Record Type: Journal Article
• Authors: Popat, Sanjay; Grohé, Christian; Corral, Jesus; Reck, Martin; Novello, Silvia; Gottfried, Maya; Radonjic, Dejan; Kaiser, Rolf
• Is Part Of: Lung cancer. Volume 144(2020)
• Page Start: 76
• Page End: 84
• Publication Date: 2020-06
• Subjects: Ab antibody -- ABC atezolizumab, bevacizumab and chemotherapy combination -- ANG2 angiopoietin 2 -- APC antigen-presenting cells -- αPD-1 anti-programmed cell death protein 1 -- αPD-L1 anti-programmed death ligand-1 -- Arg1 arginase 1 -- β2M beta-2 microglobulin -- CCL C-C-motif chemokine ligand -- CI confidence interval -- CSF1 macrophage colony-stimulating factor 1 -- CTL cytotoxic T lymphocyte -- CTLA-4 cytotoxic T-lymphocyte antigen 4 -- CXCL12 C-X-C-motif chemokine ligand 12 -- DC dendritic cell -- DCR disease control rate -- EC endothelial cell -- ESMO European Society of Medical Oncology -- FASL Fas ligand -- GM-CSF granulocyte–macrophage colony-stimulating factor -- HLA human leukocyte antigen -- IDO indolaimine-2, 3-deoxygenase -- IFN interferon -- IL interleukin -- JAK Janus kinase -- LAG3 lymphocyte activation gene 3 -- M2 Mɸ type II macrophage -- MDSC myeloid-derived suppressor cell -- MHC major histocompatibility complex -- NF-κB nuclear factor kappa B -- NSCLC non-small cell lung cancer -- ORR objective response rate -- OS overall survival -- PD-1 programmed cell death protein 1 -- PD-L1 programmed death ligand-1 -- PD-L2 programmed death ligand-2 -- PFS progression-free survival -- PGE2 prostaglandin E2 -- PS performance status -- RECIST Response Evaluation Criteria in Solid Tumors -- STAT signal transducer and activator of transcription -- TAM tumor-associated macrophage -- TCR T-cell receptor -- TEM effector memory T cell -- TGFβ tumor growth factor beta -- TGR tumor growth rate -- TIM3 T-cell immunoglobulin and mucin domain-3 -- TME tumor microenvironment -- TNF tumor necrosis factor -- Treg regulatory T cell -- VEGF vascular endothelial growth factor -- VEGFR vascular endothelial growth factor receptor -- VISTA V-domain immunoglobulin suppressor of T-cell activation; Anti-angiogenic drug -- Immunotherapy resistance -- Nintedanib -- Non-oncogene-addicted non-small cell lung cancer (NSCLC) -- Tumor microenvironment (TME) -- Vascular endothelial growth factor (VEGF); Lungs -- Cancer -- Periodicals; Lung Neoplasms -- Abstracts; Lung Neoplasms -- Periodicals; Poumons -- Cancer -- Périodiques; Lungs -- Cancer; Periodicals; Electronic journals; Electronic journals; 616.99424
• DOI: 10.1016/j.lungcan.2020.04.009
• Languages: English
• ISSNs: 0169-5002

Abstract

Highlights: The majority of patients with advanced NSCLC relapse on immunotherapy. Evidence on optimal systemic therapy after progression on immunotherapy is limited. Targeting VEGF-promoted angiogenesis may reduce immunosuppression. Anti-angiogenics may reinstate and enhance the effect of subsequent therapies. Abstract: The introduction of licensed front-line immunotherapies has heralded a new era for the treatment of non-oncogene-addicted, advanced non-small cell lung cancer (NSCLC). Yet as with all evolutions in clinical management, changes in practice can outpace the availability of the clinical evidence needed to inform subsequent therapeutic decision making. At the time of writing, there is limited available evidence on the optimum therapeutic options after progression on immunotherapy. Further research is needed to define mechanisms of immunotherapy resistance in patients with advanced NSCLC, and to understand the implications for subsequent treatment response. Pending the availability of robust clinical data and proven therapeutic options to underpin an optimized therapeutic pathway after progression on immunotherapy, attention must turn to the potential utility of currently licensed agents and any available supporting clinical data in this setting. Within this context we review the mechanistic arguments and supporting evidence for the use of anti-angiogenic agents as a means of targeting immunosuppression within the tumor microenvironment. We consider whether VEGF inhibition may help to normalize the tumor vasculature and to address immunosuppression – reinstating, and potentially enhancing, the effect of subsequent therapies. We also highlight evidence needs and signpost ongoing trials that should enable current clinical opinion in this area to be replaced by robust, evidence-based guidance.