Precision Medicine: the Promise vs. the Reality
Scientists find great potential in using genetic sequencing to help direct targeted cancer therapy, but practicing oncologists see some important limitations.
The idea of precision medicine has inspired cancer scientists and spurred a new type of cancer clinical trials — based on genes and biomarkers rather than tumor type.
But the uncertain promise of precision medicine in cancer care can be seen in two examples.
Woods Brown came to the University of Michigan Comprehensive Cancer Center with prostate cancer that had spread to his bones, lung and liver. Genetic sequencing uncovered a mutation in the BRCA2 gene. He enrolled in a clinical trial in which he received abiraterone, a standard therapy for prostate cancer, plus a PARP inhibitor, a new targeted therapy that has shown success against BRCA2 mutations.
His liver metastases shrank and his PSA dropped to near zero. He’s been in remission with no sign of cancer for more than three years.
One floor above at the Cancer Center, a patient with metastatic triple-negative breast cancer was running out of standard treatment options. She underwent genetic sequencing that suggested a PARP inhibitor would be effective, but in her case the disease progressed within a few weeks of being on the treatment.
As precision medicine gains more traction, limitations clearly remain. For starters, why do some patients have long-lasting responses that look like a cure, while other patients have little success?
“Generally, these responses are not long-lived. But when we find the right combination of agents matched to the right combination of mutations, it can lead to durable responses,” says Arul Chinnaiyan, M.D., Ph.D., director of the Michigan Center for Translational Pathology.
Promising early results
Chinnaiyan started a program at Michigan Medicine in 2010 called Mi-ONCOSEQ, which involves sequencing the DNA and RNA of metastatic cancers and normal tissue to identify alterations that could help drive treatment. About 2,300 patients — adults and children with a variety of cancer types — have had their tumors sequenced through the program.
Results from Mi-ONCOSEQ have demonstrated how precision medicine can potentially help direct cancer treatment. Of 102 pediatric cancer patients sequenced, 25 percent received a recommended novel therapy, which resulted in 10 percent of patients achieving a partial or complete remission lasting six month or longer.
“These patients should be sequenced for potential impact on treatment. We hope to make it commonplace for patients to have a molecular blueprint of their tumor to guide treatment choices,” Chinnaiyan says.
Clinical trials increasing — more needed
Indeed, an increasing number of patients are enrolling in clinical trials based on genomic sequencing. Researchers recently reported that 72 percent of the first 500 patients enrolled in Mi-ONCOSEQ harbored some kind of genetic anomaly that was clinically actionable, meaning treatments exist to target that specific aberration. While only a portion of those patients could enroll in a trial based on other eligibility factors and trial location, enrollment doubled from about 5 percent of patients in 2012 to 11 percent in 2016.
Increased trial enrollment occurred as several major national trials based on next generation sequencing opened. Researchers note that the possibility of receiving a targeted therapy based on gene sequencing is influenced by the number of available clinical trials. In the federally funded NCI-MATCH trial, the chance that a patient will match to a clinical trial is about 1 percent per trial arm open, says Anne Schott, M.D., associate director of clinical research at the Cancer Center.
“The more trials you have for more genes, the more likely you are to find a match. You have to have the trials available,” she says.
But for Schott, a medical oncologist who sees patients with breast cancer, it’s not that simple.
“I practice in the brick and mortar of the Cancer Center. I have to deal with the reality of a patient with a lethal disease in front of me and translate this promise into something that might be meaningful to them,” Schott says.
One major issue is cost. Insurance does not always reimburse for commercial sequencing tests, which could leave patients on the hook for a bill that’s typically $4,000 to $6,000. (Mi-ONCOSEQ is run as a research study at Michigan Medicine at no cost to patients.)
Then, if a patient matches to an experimental or off-label drug, insurance might not cover the drug. Targeted therapies are in the range of $10,000 or more per month.
“This is one of the realities we face with enacting precision oncology: Who pays?” Schott says.
In addition, the field is evolving so rapidly that even an active clinical researcher like Schott can’t keep up. Of the roughly 50 targeted therapies that are FDA-approved, Schott says she has prescribed only nine.
Despite the promise of precision medicine, she says, treatments prescribed based on the specific tumor type, and not for a gene mutation, will likely remain the best option for many patients.
“I believe in pursuing this line of research, but we need to pursue carefully,” Schott says. “It’s not the be-all, end-all for all of our patients. I hope these trials will tell us the subset of patients for which precision medicine will work.”