Michael Kelley, M.D., head of VA’s National Oncology Program Office
DURHAM, NC — Michael Kelley, MD, is on a mission, speaking to VA physicians across the country, spreading the word about precision oncology.
Specifically, he wants VA physicians to know about VA’s National Precision Oncology Program (NPOP). Led by VA’s National Oncology Program Office, of which Kelley is the director, NPOP documents best practices when it comes to genetic testing and helps doctors in the field figure out what the best treatment is for their patients.
After finishing his residency at the Durham VA in 1988, Kelley spent a little over a decade at the National Cancer Institute (NCI) where he took his interest in the intersection of oncology and molecular biology to the next level.
“That’s where it really became obvious that a deeper understanding of biology can drive clinical practice, though that took a while to evolve into actual clinical practice,” Kelley explained. But evolve it has, and over the last 20 years researchers have learned that understanding the specifics of a patient’s tumor can help predict just what therapies will work best to fight it.
“At its core as it’s currently practiced, precision oncology uses DNA sequencing, protein analysis and other types of assays to assess what’s happening in the tumor and the patient’s immune system,” Kelley said. “Did they inherit a certain genetic variant? That may have implications for their treatment as well. And this understanding has been exponentially expanding.”
The first big breakthrough in precision oncology hit the field just as Kelley was leaving NCI to return to the Durham VA. Researchers found that the majority of patients with a type of blood cancer called chronic myelogenous leukemia (CML) possess an abnormal chromosome created when two separate chromosomes break apart and the pieces swap places. This discovery eventually led to the creation of a drug (imatinib) that could block the abnormal gene. The result was that a cancer that once was considered a death sentence is now easily treatable, with patients going into remission and eventually demonstrating the same life expectancy as those without cancer.
Other discoveries followed, though most are not quite so clear-cut or dramatic as with CML and imatinib.
“It’s been a continuing discovery process of additional genetic alteration, modifications and refinement of understanding,” Kelley explained. “What happened next is that we understood it was not quite as simple as we drew the picture. Find a gene, take this drug, and everybody’s fine. There’s a lot more complexity to it. We chip away at the complexity and how to use more information from tumors, from the germ line of a patient, in order to make better decisions.”
For example, a small number of men with metastatic prostate cancer (about 10%) have been found to carry the BRCA2 mutation—a gene mutation also linked to breast and ovarian cancer. Their tumors have been found to respond to a class of drugs that otherwise would not be prescribed for prostate cancer.
“Last year, the FDA approved this class of drugs for prostate cancer, and VA was already starting to set up the infrastructure to test all the men who have metastatic prostate cancer for this variant in their tumors and their germ line, so we know what options work best for each man,” Kelley said.
However, while the science is complex, the decision for individual clinicians always comes down to a binary one—to use a specific treatment or not. With the constant growth of the field and the flood of new information, it’s difficult if not impossible for a practicing VA oncologist to keep up.
That’s where the National Precision Oncology Program comes in. Any physician in the VA system can request a precision oncology consult to get advice on whether a patient and treatment are a good match. NPOP also allows physicians to arrange for the right kind of testing to be performed so they have the best information possible.
“Our service will look through the patient’s medical record and results of the [testing]. And, if needed, we’ll find a specialist in that particular genetic alteration,” Kelley said. “And then we’ll be able to report back to the treating physician what our binary recommendation is.”
The program office also hosts the Molecular Oncology Tumor Board—a monthly call for VA oncologists to review cases, treatments and share information.
“It allows us to be able to discuss cases in a way which is both educational and directed toward helping the clinician make good decisions for their patients,” Kelley said. “Hundreds of people join this conference every time we put it on. We try to educate people in the field and let them get to know us so they know how we can help them help their patients.”
While new discoveries in the field of precision oncology arrive every day, Kelley also is looking ahead to a relatively new field—immunotherapy. This is a type of cancer treatment that helps a patient’s immune system fight the disease. This field has shown some impressive early results, particularly with regard to lung cancer. Immunotherapy treatments and work in precision oncology have driven the death rate from lung cancer down in recent years.
“The discussion used to be, ‘I can treat this a little, but it’s not very effective.’ Now the discussion is, ‘I can’t guarantee you that this is going to cure you, but there’s a possibility,’” Kelley explained. “It’s gone from…, a very grim diagnosis, and now there’s at least some hope that some patients will be long-term survivors of metastatic lung cancer.”
This kind of medical revolution—both in immunology and precision oncology—not only improves a patient’s chances, it also helps make sure that physicians and patients do not waste precious time in treatments destined to fail.
“These [discoveries] have definitely changed the conversation,” Kelley said. “We want to predict who would respond to what therapy, so we don’t waste time on therapies unlikely to work.”