Factors influencing the choice of treatment

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

Targeted therapy such as everolimus, sunitinib for pancreatic NETs [neuroendocrine tumors], and other therapies could again be considered in the second and third line settings where the disease develops, especially when dealing with disease outside of the liver. In patients with liver-predominant disease, we’d like to try a liver-directed approach, but we want to be careful because if it’s a high disease burden, it could actually cause harm to the patient. It is a combination of knowledge of the side effect profile of these drugs and knowledge of the patient and their situation. In a patient with poorly controlled diabetes, you may not want to start with an mTOR inhibitor. Understanding the patient as well as the medications can be very important in enabling us to select the best therapies for that patient.

One of the most important biomarkers we have, and the most important biomarker we have, in neuroendocrine cancers is the presence of the somatostatin receptor. The way we look for this is to do a Gallium-68 DOTATATE scan. I tell my patients that 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 outside of the cell. This is important for 2 reasons. First, we know that the presence of the somatostatin receptor is a good prognostic feature. The brighter, the more indolent or the better the outcome for these patients as opposed to those who tend to be somatostatin receptor negative. These tend to be FDG [fluorodeoxyglucose] ANIMALS [positron emission tomography]-positive, and these portend a kind of potentially more progressive or aggressive biology. The first reason is that it is important for prognostic benefit.

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

Transcript edited for clarity

Martin E. Berry