Neuroendocrine Tumors: Factors That Inform Therapy Selection

Diane Reidy-Lagunes, MD: In our patients who have stage IV unresectable neuroendocrine disease, treatment options and selection can be challenging for the oncologist. There are a couple of predictors that we use, or a couple of clues we use, to better define the best treatment for the patient we’re caring for. Generally, first-line treatments are somatostatin analogues because they are so well tolerated. Second-line therapies are based on a couple of features. In a patient who has a higher burden of disease, where you want some good tumor shrinkage, we often try to go to a therapy where we know that response rates are higher. For example, in the so-called foregut neuroendocrine cancers, cancers of the pancreas, lung, stomach, and duodenum, those tumors can be quite responsive to oral chemotherapy such as 5-FU [fluorouracil]-based therapies or capecitabine plus Temodar [temozolomide], sometimes even other cytotoxic therapies such as oxaliplatin-based therapies. If you want tumor shrinkages in a high burden of disease, cytotoxic therapies could be considered. 177Lu-DOTATATE is another option in those patients where response rate is something that we want to consider. We know that response rates can be higher in those patient populations than the so-called targeted therapies, which are very good at stabilizing the disease and cause some tumor shrinkage but not as much as the cytotoxics or the PRRT [peptide receptor radionuclide therapy].

Targeted therapy such as everolimus, sunitinib for pancreatic NETs [neuroendocrine tumors], and other therapies again could be considered in the second- and the third-line setting where we have disease growing, particularly when it’s disease outside the liver. In patients with liver predominant disease, we’d like to try to do a liver-directed approach, but we want to be careful because if it’s a lot of burden of disease, that could actually cause some harm to the patient. It’s a combination of knowing the adverse event profile of those drugs, and knowing the patient and what their situation is. In a patient with poorly controlled diabetes, you may not want to start with an mTOR inhibitor. Understanding the patient as well as the drugs can be very important in allowing us to select what therapies are best for that patient.

One of the most important biomarkers we have, and the most important biomarker that we have, in neuroendocrine cancers is the presence of the somatostatin receptor. The way that we look for that is by doing a Gallium-68 DOTATATE scan. I tell my patients we want the tumors to light up like a Christmas tree because if those tumors are very bright that suggests there are a lot of receptors on the outside of the cell. That’s important for 2 reasons. First, we know that the presence of the somatostatin receptor is a good prognostic feature. The brighter it is, the more indolent or the better the outcome of those patients as opposed to those that tend to be somatostatin receptor-negative. Those tend to be FDG [fluorodeoxyglucose] PET [positron emission tomography]-positive, and those portend a sort of potentially more progressive or aggressive type of biology. The first reason is it’s important for prognostic benefit.

The second is that it can actually tell us exactly where the disease is. And most importantly, it helps us ensure that we can use therapeutic options such as 177Lu-DOTATATE, which will bind to that receptor. I tell my patients when that therapy binds to that receptor, the radiation gets internalized and then it zaps the cancer, and it can actually result in tumor regression as well. It is an incredibly important biomarker, not only from a prognostic perspective, but also to allow us therapeutically to use therapies such as 177Lu-DOTATATE.

Transcript Edited for Clarity