Stanford Cancer Institute News

Fall 2017

Pamela Kunz, MD,  Assistant Professor of Medicine – Oncology, SCI member

Clinical Trial Advances Treatment Of Neuroendocrine Tumors

SCI Researchers Help Show Efficacy of New Cancer Drug

Patients with advanced neuroendocrine tumors (NETs) may soon have a new treatment option, thanks to research conducted with support from the SCI. The phase 3 Neuroendocrine Tumors Therapy (NETTER-1) trial, which involved SCI researchers, concluded that the drug 177Lu DOTATATE lengthened survival of patients with small intestine NETs by nearly three years. The results were published in the January 2017 issue of the New England Journal of Medicine.

“This is an especially exciting result,” said Pamela Kunz, MD, an Assistant Professor of Medicine – Oncology, SCI member, and author of the paper. “This has never been seen with other therapies for this disease; most other approved treatments have an absolute improvement of six to eight months.”

NETs are rare cancers that arise from cells of the endocrine or nervous system, which are found throughout the body. The most common locations for NETs are the lungs and gastrointestinal system. While most NETs are slow-growing, they can often go undetected for years, until they have already started to spread.

Octreotide, a drug commonly used to treat NETs, works by binding to the somatostatin receptor that’s found on the surface of most NETs. “It fits like a lock and key and slows down the cancer,” explained Kunz.

177Lu-DOTATATE is based on a similar molecule to octreotride, except it also packs a powerful punch of radiation. In addition to fitting into the somatostatin receptor, the drug delivers radiation to the tumor. “This drug delivers radiation in a very targeted way to NETs; this is really the quintessential definition of a targeted radioisotope therapy,” Kunz said.

In the NETTER-1 trial, 229 patients with neuroendocrine tumors at 41 hospitals around the world were assigned to receive either high-dose octreotide alone, or a combination of standard-dose octreotide and 177Lu- DOTATATE. The study included 18 patients receiving their treatment at Stanford. After 20 months, 65 percent of those who had received 177Lu-DOTATATE were alive and their tumors had not grown, while the progression-free survival rate was less than 11 percent in the control group. After the same amount of time, 18 percent of patients receiving 177Lu-DOTATATE had their NETs shrink or disappear, while only three percent of those taking only octreotide had this response.

“This treatment is well tolerated and has the best chance of delaying progression. It is a significant advancement for patients with NETs, and for their families. This treatment is also an important contribution to the field,” said Kunz.

Similar molecules to DOTATATE, but bound to the radioactive molecule 68Ga instead of 177Lu, can be used for imaging studies to show exactly where NETs are located in the body, and combining these scans with targeted drugs like 177Lu-DOTATATE enables physicians to pinpoint who will benefit most from the treatment.

“This therapy is a great example of the emerging field of theranostics, in which we can both image and treat patients based on the same molecular target,” said Erik Mittra, MD, a Clinical Associate Professor in the Department of Radiology and SCI member who also worked on the NETTER-1 trial. “That, in turn, is exactly in line with the concept of precision medicine.”

Further work will aim to determine whether the drug works well in other types of NETs, demonstrate how it influences patients’ quality of life or overall survival, study side effects in more detail, and pinpoint how 177Lu-DOTATATE should be used in conjunction with other treatments.

“It has been a long road getting this compound to market, and the excellent results of the NETTER-1 trial are a great outcome of all the work that many people around the world have put in for many decades,” said Mittra.