Orlando, FL—Physicians need to advocate for molecular profiling, according to Howard "Skip" Burris III, MD.
"I do think, in treating our metastatic patients, it's going to be as good as the next PET/CT [positron emission tomography/computed tomography] scan, and it's certainly going to be more important than the follow-up PET/CT scan that you get when the patient develops resistance or progression," he said at the 2016 Community Oncology Conference.
But the problem is cost, he added. "I think among the list of things we have to advocate for in community oncology is how molecular profiling is going to be paid for, but the cost of this needs to be determined," said Dr Burris. "I think the simple problem is, they'll pay for a test when you get an answer, but in this setting the test provides a lot of potential answers, but no definitive answer, which makes it very hard."
What Test Do I Order?
In addition to the cost, other challenges involved in molecular profiling include determining what type of test to order and knowing which technology is needed for comprehensive tissue testing, interpreting the tests and what the results might mean, determining when to rebiopsy, and getting enough tissue and prioritizing the use of that tissue.
Alterations can occur within a chromosome or across 2 chromosomes, "so there's a variety of opportunities for drug development, but it becomes all the more important to know what you're actually treating in a patient," said Dr Burris, President of Clinical Operations and Chief Medical Officer at Sarah Cannon Research Institute.
Somatic and germline mutations are important to consider as well, as more and more germline mutational abnormalities are being discovered in patients with metastatic cancer.
"But there's a lot of competition in this space, and we're going to see the best emerge," said Dr Burris.
Routine single-marker molecular tests, such as immunohistochemistry (IHC), polymerase chain reaction (PCR), and fluorescence in situ hybridization (FISH), have been used for decades and will continue to play an important role in cancer diagnosis. A multigene "hot spot" test can identify prespecified mutations occurring in very limited areas of genes of interest, but could fail to detect all classes of genomic alterations.
According to Dr Burris, a comprehensive genomic profiling approach, which tests all of the known clinically relevant cancer genes for all classes of alterations, will provide the most inclusive answer.
"I think the temptation is to get the single-marker molecular test," he said. "But what we really want to know, if cost isn't an issue, is the complete genetic profile, or what the patient had at the beginning and what they have acquired. I think that's going to be the key for us in taking care of these patients."
He warned that a new biopsy might be needed before profiling, as a patient's tumor may change over time depending on treatments and can acquire therapy-specific resistance mutations, so the molecular status of an historical sample may not reflect the patient's current disease status.
More Liquid Biopsy on the Horizon
Although tissue-based assays are still the "gold standard," according to Dr Burris, liquid biopsy—a new noninvasive technique that can detect disease biomarkers in blood, urine, and other body fluids—is going to be key in the near future. "Many of your patients don't have disease accessible to biopsy, so liquid biopsy is where it's heading," he said.
It seems that highly specific tests are more sensitive than broad-based tests and could be adopted much quicker (eg, Droplet Digital PCR–based tests are more sensitive than tests based on next-generation sequencing), he said, but currently there are biologic challenges to be addressed (eg, heterogeneity, localization, not all clonal events are cancer). In addition, 42% of patients shed no detectable circulating tumor DNA into the bloodstream, which Dr Burris called "a little discouraging."
JP Morgan predicts liquid biopsy will be a $20-billion field in the next 5 years, "but figuring out how to pay for it will be an interesting challenge," Dr Burris said.
"We're taking care of the other 99% that can't get the Dana-Farber or the MD Anderson treatment. They're being treated in the community, and how we do this is so important," he said. "We've got to find the right therapy for the right patient at the right time, and I think biopsy, identification, profiling…all of these are going to be very key."
Burris HA. The influx of new cancer drugs: clinical, patients care, and operating ramifications. Presented at: 2016 Community Oncology Conference; April 14-15, 2016; Orlando, FL.