6533b7d3fe1ef96bd1260b6e

RESEARCH PRODUCT

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?

Jesus CorralSanjay PopatSanjay PopatSilvia NovelloMartin ReckDejan RadonjicRolf KaiserMaya GottfriedChristian Grohé

subject

0301 basic medicinePulmonary and Respiratory MedicineOncologyCancer Researchmedicine.medical_specialtyLung Neoplasmsmedicine.medical_treatmentNintedanibContext (language use)Angiogenesis InhibitorsAnti-angiogenic drugNon-oncogene-addicted non-small cell lung cancer (NSCLC)03 medical and health scienceschemistry.chemical_compound0302 clinical medicineInternal medicineCarcinoma Non-Small-Cell LungmedicineTumor MicroenvironmentHumansTumor microenvironment (TME)Lung cancerImmune Checkpoint InhibitorsTumor microenvironmentAnti-angiogenic drug; Immunotherapy resistance; Nintedanib; Non-oncogene-addicted non-small cell lung cancer (NSCLC); Tumor microenvironment (TME); Vascular endothelial growth factor (VEGF)Oncogenebusiness.industryVascular endothelial growth factor (VEGF)ImmunosuppressionImmunotherapymedicine.diseaseImmunotherapy resistance030104 developmental biologyOncologychemistry030220 oncology & carcinogenesisNintedanibNon small cellImmunotherapybusiness

description

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.

https://hdl.handle.net/10171/66755