Precision medicine experts at Sylvester Comprehensive Cancer Center are applying advances in cancer genetics – specific mutations that occur across tumor types and locations – to match people to therapy that targets the mutation driving their cancer.
“At Sylvester we are unique in South Florida in our ability to internally and rapidly identify the driver mutations in an individual patient’s tumor, then use the information to enroll the patient to a clinical trial that may have a higher probability of success,” said Jonathan C. Trent, M.D., Ph.D., medical director of Sylvester’s precision medicine initiative and professor of medicine at the University of Miami Miller School of Medicine.
“Our Molecular Tumor Board has reviewed 300 patient cases, and of those we’ve been able to get 25 percent on targeted therapy,” said Bat-ami Katzman Gordon, director of precision medicine at Sylvester. For reference, the expectation is that only 10 percent of cases have mutations targetable with available treatment.
Most of the patients present with rare or late-stage cancers, making the Molecular Tumor Board’s task more challenging and more critical at the same time. Many of the uncommon tumors have no standard of care or definitive plan of action. “Our typical patient has late-stage cancer and they’ve run out of options,” said Jared Cotta, M.P.H., project coordinator at Sylvester.
Patient case presentations are often complex. “We’ve seen patients with two primary cancers and we work to find a solution to treat both, based on the genetic changes seen in both,” Gordon said. In addition, the Molecular Tumor Board assessed a patient initially diagnosed with two distinct tumors who turned out to have a primary malignancy and a metastasis instead. Tumor DNA analysis not only led to additional treatment options but increased the diagnostic precision in this case.
The Tumor Board also reviewed the case of a patient with a rare tumor in her brainstem. A biopsy was not possible because of the location. However, the patient had a metastasis that could be evaluated, and it revealed a mutated gene, common in melanoma, that had an effective therapy option.
“She’s been on therapy now over two years. At that time she was not able to walk or talk, but she’s doing both now,” Gordon said.
Cancers have been classified and treated for decades based on their location in the body. But advances in genetics research have the potential to change that.
“Sylvester’s precision medicine approach allows us to treat patients with therapies targeted to the specific mutation driving their cancer,” said Trent, who is also co-director of the Musculoskeletal Center, Sarcoma Medical Research Program. “If the same cancer-causing mutation leads to melanoma, sarcoma, and liver cancer, why not treat all of these with a medicine that targets that cancer-causing mutation?”
In other words, biomarkers like HER2 are no longer only relevant to breast cancer. Researchers observe the same genetic changes in gastric and other cancers. And this is ushering in an era of enhanced precision with interventions targeted to the genetic profile of an individual’s tumor instead of its location.
“We’re looking to apply those genetically driven therapies to all cancer types,” Gordon said.
The Molecular Tumor Board refers many patients to cutting-edge cancer studies, taking advantage of Sylvester’s clinical trials program. “Since we have such a robust clinical trial portfolio, we serve in a sense as a liaison between physicians, their patients and the clinical trial network we have here,” Cotta said.
Two of the more high-profile precision medicine oncology trials in the United States are available at Sylvester. These are the National Cancer Institute’s MATCH trial and the American Society of Clinical Oncology’s TAPUR study. “The TAPUR trial is more like 14 trials in one, with 14 different therapeutic arms based on specific cancer mutations,” Gordon said. “Sylvester is the only available site in Florida for the TAPUR study.”
“We have a couple of people on the MATCH trial who have been on treatment for over a year now,” says Cotta.
Trent added, “Over a year with stable disease or without disease progression is a success when you’re a patient with late-stage cancer who previously had no options.”
The Sylvester Molecular Tumor Board is multidisciplinary by design. “We’re integrating the experience from the physicians who have been using targeted therapies in one cancer type and applying it to many,” Trent said. “So we use our vast multidisciplinary experience across cancer types to treat patients better.”
“Because treatments have been location-based until now, breast cancer specialists know HER2 better than anyone else, and others know the ways certain therapies work,” Gordon said. “It’s important to understand that not only does the patient have a target we have a drug for, but what does that mean – is that drug particularly hard on the patient? Are there specific side effects to be aware of? What happens if the patient is not doing well – is there an alternative way to administer the drug?” This is critical information that can only come from experience.
Tumor genetics has advanced rapidly since the Tumor Board reviewed its first case in early 2016. The Food and Drug Administration has approved a significant number of targeted therapies for new indications since then. In May 2017, for example, the agency approved Pembrolizumab as the first-ever cancer therapy based on a biomarker.
“The field is changing so rapidly that some agents we recommended initially as off-label treatments are now FDA approved,” Cotta said.
The precision medicine group is also now incorporating some of the cancer biology faculty and Ph.D. candidates to help the clinicians stay up-to-date on new therapies and new clinical trials, Gordon said. “We’re reaching across the university to increase the collaboration and resources available to our patients and their treating physicians.”
The Tumor Board hopes to keep expanding its patient base. “We would like to offer participation to community oncologists,” Cotta said. “One of our visions for the future is to be able to expand along with our international group, so we can offer consultations to individuals who don’t have precision medicine resources at their facilities.”