Rationale Behind Antiangiogenic Therapy in NSCLC

Transcript:

Benjamin P. Levy, MD: We are just beginning to learn about how VEGF elaboration from tumors may foster an immunosuppressive environment. In at least preclinical models, VEGF upregulates regulatory T cells. It upregulates myeloid-derived suppressor cells. It also decreases T-cell trafficking. When there’s VEGF around the tumor, there’s a good chance that the tumor in and of itself may be immunosuppressive and less likely to be recognized by the immune system, which is all the more rationale as to why we’re looking at targeting VEGF with antiangiogenic strategies with immunotherapy.

Ann Tsao, MD: In metastatic non—small cell lung cancer, we know that tumors need to feed themselves. They do this by producing certain proangiogenic factors, like vascular endothelial growth factor, VEGF. We do know that targeting this angiogenic pathway using antiangiogenic inhibitors can be beneficial for our patients.

The antiangiogenic inhibitors have various modalities, some of which are monoclonal antibodies, some of which are tyrosine kinase inhibitors. The monoclonal antibodies work by taking VEGF or serum VEGF out of circulation. Essentially, it breaks that pathway’s bond between the ligand and the receptor, and that’s usually the way it works to inhibit angiogenesis.

Benjamin P. Levy, MD: Antiangiogenic strategies have come a long way for lung cancer. We know that antiangiogenic strategies, drugs that target the VEGF ligand and the VEGF receptor, help reverse much of the dysregulation that occurs in tumor vasculature. When we target VEGF by delivering these drugs, we’re allowing drugs to be better delivered to the tumor. Those drugs may be chemotherapy or they may be immunotherapy, but it allows for a reversal of the disruption of these vessels and allows for better drug delivery.

The VEGF TKIs have been tested quite a bit in advanced non—small cell lung cancer. Several of these drugs—nintedanib, vandetanib, sunitinib, sorafenib—are all oral therapies. Unfortunately, when these drugs have been evaluated, they’ve been looked at in combination with chemotherapy in an unselect patient population with advanced non–small cell lung cancer and also in a chemorefractory setting in combination with docetaxel and other drugs. These drugs, for better or for worse, just haven’t demonstrated meaningful improvements in overall survival. I think there was a lot of hope that these drugs would work. There was a lot of scientific rationale as to why they may work. While nintedanib does have an approval in Europe based on a subset analysis in an adenocarcinoma population, it doesn’t have an approval here. None of the VEGF TKIs are currently approved for advanced non–small cell lung cancer.

Transcript Edited for Clarity