James C. Yao, MD
It’s been an exciting year thus far for patients with neuroendocrine tumors (NETs), with the FDA approving a new treatment regimen and more advancements on the horizon, according to James C. Yao, MD, a professor in the Department of Gastrointestinal (GI) Medical Oncology at The University of Texas MD Anderson Cancer Center.
at the 2016 World Congress on Gastrointestinal Cancers in July to discuss developments in the field.
OncLive: Please summarize the highlights of neuroendocrine advancements.
: The last year has been a big year for neuroendocrine tumors. There were 3 positive phase III studies. One included everolimus in lung and GI neuroendocrine tumors; that study has already been published in Lancet in March.1
It received the FDA approval late in February.
The study showed a significant decrease in bowel movement count. It is less than, on average, 1 BM per day from their baseline. But nonetheless, it was a positive study. Publication and health authority decisions are still pending.
What can you tell us about next-generation somatostatin analogs, particularly pasireotide?
The current generation of somatostatin analogs mostly target somatostatin receptor-2 and, to some extent, somatostatin receptor-5, and these are octreotide and lanreotide. There are new agents on the horizon that target a broader profile of somatostatin receptors. These include pasireotide, which targets somatostatin receptors 1,2,3, and 5. Its utility in refractory carcinoid syndrome was also explored in a phase III study, but because of the study design and the limited number of patients, I don’t think this study really fully answered the question.
Nonetheless, in that study there were some hints that it may have some efficacy in terms of further delaying disease progression compared with regular somatostatin analogs. Whether those will be explored in future trials remains an unanswered question at this time.
Where does telotristat etiprate fit in?
Telotristat is a little bit different. It doesn’t target the somatostatin receptor, but specifically serotonin. So I really think this is going to be limited to control refractory diarrhea.
There are 2 components for carcinoid syndrome, and that’s flushing and diarrhea, with serotonin being the one that’s responsible for the diarrhea component. So that’s where telotrisat will likely have its role—in patients with refractory diarrhea from neuroendocrine tumors.
What is the potential for PRRTs in development for NETs?
Peptide receptor radiotherapy is using this somatostatin receptor in a different way. You can use the ligand in the peptide, in this case to deliver a radioisotope to the tumor.
Because some of the isotopes that are being used include indium, yttrium, and lutetium, the agent probably best studied is the lutetium label compound. That’s what the NETTER-1 study was about. Previously, there have been a lot of single-arm case series or potentially single-arm studies showing activity. NETTER-1 showed a randomized control study for midgut neuroendocrine tumors and the utility of PRRT in this group of tumors in delaying tumor growth.
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