Paul R. Helft, MD
Since the FDA approval of Lutathera (lutetium Lu 177 dotatate) in January 2018, other treatments may take a backseat to peptide receptor radionuclide therapy (PRRT) for patients with gastroenteropancreatic (GEP)-neuroendocrine tumors (NETs), says Paul R. Helft, MD. The reason is that because Lutathera can concurrently treat multiple sites of disease, it could be the dominant therapy in this space.
The approval was based on results from the phase III NETTER-1 trial, which showed a 79% reduction in the risk of progression or death with Lutathera compared with octreotide (Sandostatin) in patients with midgut NETs. The overall response rate with Lutathera was 13% versus 4% with octreotide (P
<.0148). The overall survival interim analysis showed a 48% reduction in the risk of death with Lutathera versus octreotide (HR, 0.52; 95% CI, 0.32-0.84).
Moreover, findings of small studies have confirmed the efficacy of combination therapy with capecitabine (Xeloda) and temozolomide (Temodar) as well. But regarding progress with immunotherapy, Helft said that well-differentiated NETs have a fairly quiet genome, adding, “The basic markers that immunotherapy has demonstrated efficacy in are absent in GEP-NETs.”
In an interview during the 2018 OncLive®
State of the Science Summit™ on Gastrointestinal Cancers, Helft, professor of medicine, Indiana University School of Medicine, Indiana University Melvin and Bren Simon Cancer Center, discussed the incidence of gastrointestinal (GI) NETs and available and emerging treatment methods.
OncLive: Can you provide an overview of your presentation on NETs?
NETs are a group of tumors that can originate from many organs within the body, but primarily originate from within the GI tract. The majority of them start in the small intestine, followed by the pancreas. Pancreatic NETs are sometimes described as a rare group of tumors, but because they tend to be slow growing, their prevalence in the United States isn’t quite as high.
Is there a subset of NETs that is more difficult to treat than other subtypes?
There are only a few thousand new cases of reported pancreatic NETs each year. It’s a relatively rare and unique type of tumor. They are often lumped in with carcinoid tumors of the small intestine, which are much more common. Although carcinoid tumors are at least 3 to 4 times more common than pancreatic NETs, they both present various challenges.
Twenty percent to 40% of carcinoid tumors of the small intestine make hormones, the most common of which is serotonin. This causes carcinoid syndrome, which presents its own unique set of challenges in addition to the number of GI symptoms, hot flashes, etc, that patients experience. A minority of pancreatic NETs make excess hormones and can lead to very significant syndromes. Those that produce excess insulin are very difficult to manage because they cause lots of hypoglycemia. Those that produce other excess hormones can cause terrible ulcer disease.
What agents are you most excited about entering the landscape?
Even though NETs of the GI tract are not commonly talked about, they are fairly prevalent. Over the last 10 to 15 years, there have been at least 4 or 5 FDA approvals in this space. That has altered the treatment landscape. We have had somatostatin receptor analogs for some time, which enable us to treat the growth of the tumor as well as the syndromes. These new targeted therapies have really changed the treatment landscape.
In January 2018, Lutathera was approved by the FDA. It’s a complex treatment to deliver, so its uptake will probably be relatively slow. It will likely be centered at larger centers around the United States. Lutathera is a type of PRRT and is the primary antibody-connected radiotherapy in this space.
Yttrium-90 resin microspheres, or liver-directed therapy, is used more generically in these and other sets of tumors. It’s a radiolabeled glass bead, specifically a microscopic glass bead that is injected in the hepatic arterial system to treat liver tumors of various sorts. It’s used in NETs, colorectal tumors, and hepatoma.