Advanced Neuroendocrine Tumors: VEGF-Targeted Therapies

Diane Reidy-Lagunes, MD: The role of VEGF is critical in neuroendocrine cancer, and it’s one of the drivers that allows our cancers to grow and divide. In 2011, we had the first VEGF inhibitor that was approved for pancreatic NETs [neuroendocrine tumors], and that’s been an FDA indication since then. More recently, there have been other VEGF inhibitors that have been tested or are being tested, to try to improve progression-free survival and improve outcomes for our patients with these diseases. The various VEGF inhibitors include, for example, axitinib, which was a study in the phase 2 setting that showed a lot of promise. More recently, they did report on the role of axitinib with a somatostatin analogue that did not meet its progression-free survival end point, although it did show some activity, but did not reach the primary end point of the study. We have other drugs, such as surufatinib, which was recently FDA approved based on 2 studies in China. They did surufatinib in pancreatic NETs as well as extrapancreatic NETs…both of them improved progression-free survival, which was very exciting. It’s notable that surufatinib would be, at least in China, the first FDA-approved drug that is a VEGF inhibitor for extrapancreatic NETs. Remember, the sunitinib is approved for pancreatic NETs. And then Jennifer Chan, MD, MPH, is leading a study of cabozantinib, which is another VEGF inhibitor, through the NCI [National Cancer Institute] cooperative groups, and we are testing the role of that in extrapancreatic as well as pancreatic NETs.

There’s no question that VEGF is a very important driver in neuroendocrine cancers and has shown activity and promise in our diseases. What are the adverse event profiles?Most of them are hypertension, some fatigue, some proteinuria, manageable adverse effects that most of us as oncologists understand when we’re using these tyrosine kinase inhibitors. Again, it’s very mindful and important to remember in our patient population that we’re asking these questions and how they’re feeling.

What’s unique about surufatinib is that in addition to targeting the tyrosine kinase inhibitor of VEGF, it also inhibits the FGF receptor, as well as the CSF1R [colony stimulating factor-1 receptor] inhibitor. It may be that the combination of those 3 tyrosine kinase inhibitors could be more effective and more promising in our patients with neuroendocrine cancers. That new drug application was submitted to the FDA. It was approved to be submitted, and we’re hoping to hear by April of next year what the outcome is for surufatinib in the United States, based on those 2 studies, which is surufatinib in extrapancreatic, as well as surufatinib in pancreatic neuroendocrine cancers. Those were a Chinese patient population, both phase 3 data that improved the progression-free survival.

Transcript Edited for Clarity