Systemic Therapy for Advanced Neuroendocrine Tumors

Diane Reidy-Lagunes, MD: I tell my patients our goals of therapy for advanced neuroendocrine cancer that’s incurable is quality and quantity. We want to make sure that we keep our patients with us for as long as possible and thank heavens our patients with neuroendocrine cancers can live for many years and often many decades. Because of that, the quality, and the therapies that we choose are critically important. We have to be very mindful of those toxicities. Grade 1 to 2 fatigue, for example, in a patient where they’re going to be on that therapy potentially for many months, into many years is a quite significant adverse effect. Having grade 2 fatigue is a very hard thing for our patients to endure over a long period of time. We’re constantly weighing the benefits and the risks of these different therapies and being mindful about dose reducing and really being careful that we’re asking our patients how are they feeling, how are they doing? Many of our patients will do whatever we tell them to ensure that the disease stays stable. But again, we want to make sure we’re being mindful of the adverse effects that they have and that we’re treating at appropriate times. When the disease grows, we need to be on these therapies, but sometimes there are opportunities for treatment holidays that we really want to take advantage of. We can’t let our patients come back in 6 months when they’re on a treatment holiday, but we want to be mindful of the ability to potentially give our patients breaks when they need them.

Most oncologists would agree that first-line therapies are somatostatin analogues. Second-line therapy can be a bit more challenging to choose for our patients because we don’t have those clinical trials to really drive the decision of what should be done with an evidence-based approach. We use our best tools to understand the patient in front of us to better decide what those second-line therapies should be. In a patient with a higher burden of disease where response rate is something that’s important, we’ll use cytotoxic therapies. The role, for example, of peptide receptor radionuclide therapy [PRRT] is one that is critically important. It came and was finally FDA approved in the United States back in 2018. At that time, we were using it in much more advanced patient populations. Now we know that although there are very serious and concerning adverse effects, they’re pretty rare. The 2% to 3% risk of MDS [myelodysplastic syndromes] is something that we worry about. But in patients, for example, in small bowel where we’re really limited on other additional therapies after somatostatin analogue therapy, PRRT can be incredibly helpful, and I tend to use it a little bit earlier now. I will often use it actually after somatostatin analogue progression in patients who have extrahepatic disease and disease in different places where I want a really good systemic approach. Second-line therapy, for example, in a small bowel NET [neuroendocrine tumor] could be mTOR inhibitors, it could be PRRT. It comes down to adverse event profile, knowing your patient population, knowing that patient and what risks you’d be willing to take, based on their burden of disease and how well they’re doing. In the so-called foregut tumors, where you have other options, again it depends on how much response you need, how well the patient is doing, and if they’re symptomatic or not.

Transcript Edited for Clarity