Inoperable NETs: The Role of Systemic Therapy

Pamela Kunz, MD: For patients in whom curative surgery is not an option, we do think about using systemic therapies. These might be patients who either have metastatic disease at the time of diagnosis, or perhaps they’re patients who have an unresectable primary tumor given its location. They may also be patients for whom there are other medical comorbidities that prevent surgery or make it unsafe.

We have that same list of systemic therapy options, and I’ll group them into categories. There are somatostatin analogues, which include octreotide and lanreotide. Again, these do not shrink tumors but will yield tumor control. We have biologic therapies that include targeted agents, perhaps tyrosine kinase inhibitors like sunitinib, or mTOR inhibitors like everolimus. These also do not tend to shrink the tumor, but they yield tumor control or stability as a best response. We also have chemotherapies. Temozolomide and capecitabine are often used for metastatic pancreatic NETs [neuroendocrine tumors].

We also sometimes consider using these preoperatively, so if a surgeon says to me, “I really need a bit of tumor shrinkage before considering a surgery for this patient; it might make the surgery easier,” we will consider that for pancreatic NETs. Last is the use of PRRT, or peptide receptor radionuclide therapy, with lutetium 177 Lu-DOTATATE. This is also indicated and approved for patients with metastatic NETs. There are some ongoing clinical trials evaluating the use of PRRT perioperatively, also in an effort to see whether it helps shrink tumors to get patients to surgery or if it helps improve outcomes postoperatively. We’re looking at all these systemic treatments for patients who cannot undergo a curative surgery.

Transcript Edited for Clarity