Key Considerations When Treating Patients With NETs

Arvind Dasari, MD, MD Anderson Cancer Center, Houston, TX, discusses the key consideration clinicians should take when treating patients with neuroendocrine tumors. Dr Dasari highlights the importance of determining the stage, grade and differentiation of the tumor, and functional status.

Transcript:

Hello, I'm Arvind Dasari. I'm an associate professor in the Department of GI Medical Oncology at MD Anderson Cancer Center.

I think the key aspects that we take into account when making treatment decisions about patients with neuroendocrine tumors are obviously the stage, whether it's resectable or not, and patients with resectable disease would have resection.

The second thing would be a grade and differentiation of the tumor. And there's a nuance here. The classification of neuroendocrine tumors has evolved over time. Previously neuroendocrine tumors were classified into well-differentiated neuroendocrine tumors and poorly differentiated neuroendocrine carcinomas. And the cutoff for the Ki-67 between these 2 groups was 20%. What this meant, based on the prior classification, was that any patient who had a Ki-67 of over 20% was automatically poorly differentiated and synonymous with high grade neuroendocrine tumors. And the well-differentiated neuroendocrine tumors were kind of subdivided into low-grade and intermediate-grade, but for the most part they're treated the same way. But the high-grade of poorly differentiated neuroendocrine carcinomas, they were to be treated with chemotherapy regimens similar to what we use in small cell lung cancer.

With the latest classification in 2017, acknowledging these limitations, WHO further kind of sub-classified the high-grade neuroendocrine tumors into well-differentiated and poorly differentiated. So essentially what that means is that the high-grade tumors, even though they have a Ki-67 of greater than 20%, do not automatically need to be treated with these aggressive chemotherapy regimens. They could be more treated like well differentiated neuroendocrine tumors unless the morphology suggested that they had a neuroendocrine carcinoma as evidenced by large cell or small cell morphology on the histology. That's the second aspect that we want to look at.

The third thing would be the functional status, whether the patient has carcinoid syndrome or in the case of pancreatic neuroendocrine tumors, it could be excess production of insulin, glucagon, and other hormones that the pancreas typically produces. And finally, we also want to look at the extent of disease of metastatic, how bulky is the tumor.

Based on all these factors, we try to make decisions about which therapy to start with. And broadly the classes of drugs that are available currently for tumor control would be somatostatin analogs, very well tolerated, but with minimal response rates. PRRT [peptide receptor radionuclide therapy), well tolerated, moderate response rates around 15% to 20% as compared to 1% to 2% with somatostatin analogs. Tyrosine kinase inhibitors, sunitinib and everolimus, these tend to have moderate response rates and also moderate side effect profile. And finally, chemotherapy options. So temozolomide are streptozocin, more so temozolomide lately in combination with capecitabine. That's been shown to have response rates of close to 40% in patients with pancreatic neuroendocrine tumors.

You try to balance the side effect profile with the need for radiographic response in the patients that we're seeing. Also make sure that the primary site and the functional status are taken into account when making treatment decisions. Specifically with regards to functional tumors, these patients for both parts tend to be under somatostatin analog throughout their treatment course. And especially for carcinoid syndrome-related diarrhea, there is a peripheral tryptophan hydroxylase inhibitor called telotristat [ethyl]. That's an oral drug that could be added on if the diarrhea is not well controlled.

That, by and large, is the systemic therapy armamentarium that we have for these patients. And there's also the option of considering liver-directed therapies in patients who have liver dominant disease, which tends to be a lot of patients.