Conversations on COMBATING Cancer
Two new programs exemplify Stanford’s strengths in clinical care and translational research in cancer.
In recent decades it’s become increasingly clear that cancer is an incredibly complex disease. No two cancer types are exactly alike, no two patients are alike, and treating tumors involves attacking them from all angles. At Stanford, oncologists are tackling many sides of cancer research and patient care through innovative collaborations and programs. Two new programs in the Division of Oncology demonstrate this: the Neuroendocrine Tumor Program brings together professionals from many specialties to treat patients with these rare tumors; and the Phase I Clinical Research Program helps bring experimental new drugs to Stanford patients—while giving basic scientists vital research opportunities to study the drugs.
Recent conversations with the directors of the two programs convey what makes them unique and important.
To start out with, what are neuroendocrine tumors?
Neuroendocrine tumors, or NETs, are rare cancers that can originate in almost any part of the body. We most commonly see them in the gastrointestinal tract and lungs. They tend to be slower growing than other cancers; even patients with metastatic disease can live for many years. The incidence is very low—only about seven people per 100,000 are diagnosed each year in the U.S. But because many patients live for years with their disease, the prevalence is actually quite high. There are more people living with NETs in the U.S. than with esophageal, stomach, and pancreatic cancer combined.
Why is it important to have a distinct program focusing on NETs?
These are so different from other cancers; they’re really a different entity and they require different therapies. Knowing how to select the initial treatments for a patient, then tailor those treatments, requires some expertise. Because NETs are not common, a community oncologist may only see a handful of cases ever. In addition, we are especially interested in meeting the long-term needs of these patients, and we have established a new NET survivorship program focused on addressing symptoms of cancer, side effects of treatment, nutrition, and mental health.
What does managing the NET program at Stanford involve?
This disease requires complex coordination among many disciplines—medical oncology, surgical oncology, nuclear medicine, interventional radiology, endocrinology, cancer genetics, and psychiatry. So it’s really about pulling together the expertise to make sure patients get the best care. We see about 200 NET patients a year at Stanford, and they often travel long distances. We try to not only treat patients here, but partner with the patients’ oncologists back home.
Is the NET program involved in research as well as clinical care?
Yes. We have participated in many key clinical trials and other clinical research projects. This last year we participated in the study of a new drug called 177Lu-Dotatate, which delivers radiation in a very targeted way to NETs; this is really the quintessential definition of a targeted therapy. The results of our work were published in the January 2017 issue of The New England Journal of Medicine, and the drug is now being reviewed by the FDA. It will very likely be the focus of future generations of studies. We want to know whether we can combine other treatments with 177Lu-Dotatate, which patients respond best to the drug, and whether there are any long-term side effects. We are also looking for new diagnostic tests to better identify which patients may have more aggressive cancers so we can tailor selection of treatments.
What plans do you have for the NET program?
With so many new therapies for NETs, we are emphasizing patient and physician education. Three continuing medical education events in the next year will teach community physicians and other health care providers about NETs. We also host an annual NET patient education event. Lastly, we are thrilled to have received funding for a fellowship to train the next generation of NET specialists. Our first NET fellow will start in mid-2018.
How did the Phase I program come about and what are its goals?
First of all, a phase I trial is when you’re testing a drug for the first time in humans; you’re trying to figure out safety, dosing, and which patient population to target. This is the key stage between preclinical development and clinical development. I was recruited to Stanford from the National Cancer Institute in 2015 and started the phase I clinical research program for patients with advanced solid tumors. The goals are to leverage the broad clinical and research expertise that exists at Stanford and to work with various stakeholders, including industry, to develop new therapies for cancer. The program is designed to facilitate development of promising anticancer therapies while ensuring the highest standards of patient safety.
What does the Phase I program at Stanford do to help ensure quality trials?
If researchers have a molecule that they’re interested in moving forward into phase I trials, we sit down with them and go through their information, we see if they need additional data, and we talk to them about what it will take to get a trial in place. We also help identify what resources will be needed to advance the research into the clinic. Then, we help design the clinical protocols and conduct the trials. Basically, we provide expertise that bench scientists may need to translate their findings.
You also work on phase I trials coming out of industry, right?
Yes. The majority of drug discovery and development happens in industry, where they’re identifying novel targets and developing new molecules for testing. Therefore, it is very important that we build that collaboration. It gives us access to cutting-edge molecules, and it creates opportunities for our patients to participate in clinical trials of these agents and for our scientists to conduct scientific studies with these molecules.
Why are phase I trials so important?
Phase I studies are at the interface of preclinical and clinical development. It’s basically where we make the decision about whether a new drug should be moved forward into later stage clinical development. A lot of drugs go all the way through clinical development and fail to work, so it’s important to have a strong phase I program that can help prioritize promising drugs early and expedite their development.
Why is Stanford a good place for phase I trials?
Stanford is very strong in basic and translational science. The sense of innovation here makes it a great place for phase I trials. Our Bay Area location is advantageous because we are able to interface easily with companies. The phase I program provides opportunities to translate the discoveries into the clinic and facilitate the development of new treatments.
Is there a phase I trial going on at Stanford right now that you’re particularly excited about?
Currently the phase I program is investigating a number of novel agents with a variety of mechanisms of action, ranging from immune therapies to genetically targeted agents. In collaboration with Loxo Oncology, our program is involved in the development of their new drug, larotrectinib, which targets solid tumors—including brain, breast, colorectal, thyroid, and lung cancers—with a particular genetic alteration. The drug has shown a 76 percent response rate in both adult and pediatric patients with metastatic tumors. The company is moving forward toward applying for drug approval, based in part on the results observed at Stanford.