Systemic Therapy: Advanced Neuroendocrine Tumors

Matthew H. Kulke, MD: The goals of therapy for patients with advanced neuroendocrine tumors are not all that different from patients with other types of cancer. One difference might be in patients who have symptoms of hormone hypersecretion, for whom you want to control those symptoms. Often, somatostatin analogues will do that. In patients with carcinoid syndrome, another newer agent, telotristat, can also be quite helpful in decreasing serotonin that is synthesized by the tumor and that can cause many of those symptoms. Beyond that though, the goals are really the same as any other cancer. You try to make patients live longer and feel better.

Beyond somatostatin analogues, we are now looking at second- and third-line treatment options. Again, while there are lots of options, there is very little data to guide us in terms of what to use second, third, or even fourth. One of the nice things, though, is that the sequence in many cases may not matter all that much. The agents that we have all function in very different ways. In some sense, perhaps the most important thing when thinking about treating a patient is not necessarily which treatment you are using second, third, or fourth, but just making sure that your patient is going to have access to all the treatments that are currently available.

I think the placement of all these treatments remains an open question. There are randomized trials ongoing right now that are trying to tease out this question. We can think about some factors, perhaps, that might influence the choice of treatment. For peptide receptor therapy, that is a somatostatin receptor-targeted therapy, so one of the important things there is just to demonstrate that tumors do have somatostatin receptors, usually with a gallium dotatate PET [positron emission tomography] scan that will give you that answer. For some of the other treatments’ factors we might take into consideration, for a patient with advanced pancreatic neuroendocrine tumor that has a very high tumor bulk, treatment with temozolomide/capecitabine is a great option. It is associated with response rates. You might also take into consideration comorbidities. For patients with hypertension, you might need to be cautious with VEGF inhibition. For patients with diabetes, you might need to be cautious with everolimus. There are several factors, again, that we take into consideration and we try to weigh the risks and benefits for any individual patient.

Transcript edited for clarity.