Advanced Neuroendocrine Tumors: Clinical Trials With Surufatinib

Diane Reidy-Lagunes, MD: There were 2 very important and exciting studies in China in the role of surufatinib in our patients with neuroendocrine cancers. Both of those studies showed improved progression-free survival as well as response rate when compared with placebo. The first study was SANET-p, which was in patients with pancreatic neuroendocrine tumors. There were 172 patients randomized in a 2:1 setting to receive either 300 mg daily of surufatinib or placebo. That study was positive with a progression-free survival of 19.3 months in the surufatinib arm vs 11 months in the placebo arm, again leading to the FDA approval in China of surufatinib.

The second study was SANET-ep, which was patients with extrapancreatic neuroendocrine cancers. It was a 2:1 randomization where our patients on the experimental arm received 300 mg of surufatinib daily vs placebo. The progression-free survival was 9.2 months vs 3.8 months, indicating an FDA approval in China for this drug in extrapancreatic neuroendocrine cancers. It’s of note that it’s the first antiangiogenic inhibitor in extrapancreatic neuroendocrine cancers since 2011, when sunitinib was approved in the United States for pancreatic neuroendocrine cancers. Both studies showed that the adverse-event profile was consistent where it was mostly hypertension, proteinuria, and some fatigue.

The ideal patient for surufatinib would be someone who had a progressive disease after somatostatin analogue therapy, where particularly they may have disease outside the liver and need good disease control. We still need to do research into understanding who the ideal patient would be. Is there a biomarker, for example, that you’d consider for the VEGF inhibitors compared with, for example, PRRT [peptide receptor radionuclide therapy]? We don’t have that data. We’re hoping those data will come, but it’s very exciting that we have another drug to potentially consider for our patients with these diseases.

In the future we’re going to see a lot of studies that are thinking about combinations of therapies, such as surufatinib with other drugs. One could envision potentially a role with immunotherapy as we’ve seen in other disease, like where cabozantinib showed to be promising. That would be something to consider in the context of a clinical trial. We know unfortunately immunotherapies in our diseases in general have not been very helpful, unlike other solid-tumor malignancies. There could be potential for very exciting opportunities for these combinations of therapies where you have an active drug. Potentially by giving that active drug, you could add on a therapy such as immunotherapy and see if we could offer more of a promising combination. It would be exciting to see such a trial be considered.

The promise of surufatinib is 1) we’re very excited about adding to our armamentarium for our different drugs and opportunities for our patients to control these diseases. In addition to the potential to add on to other therapies in the future, it will be very important to start doing our best to understand which drugs can control the disease for the longest, while providing an appropriate adverse-event profile. To date, the drug seems to be well tolerated. If there’s something different about that in the US patient population, we don’t know. There’s a phase 1 study ongoing to test the safety of the drug in the United States, and we’re all excited about that. The role of questionnaires in terms of quality of life is very important as we do these trials and better understand the different adverse-event profiles with the efficacy of these therapies and try to weigh which ones are best for our patients.

Transcript Edited for Clarity