NEW YORK (GenomeWeb) – A precision medicine program in the New England region is aiming to test US veterans recently diagnosed with non-small cell lung cancer on next-generation sequencing panels, provide them individualized treatments, and give them the chance to participate in research.
The Precision Oncology Program (POP) is being executed by leaders at the Massachusetts Veterans Epidemiology Research and Information Center (MAVERIC) for veterans served by the New England Veteran’s Integrated Service Network (VISN 1). "The intention of the program is to primarily deliver state of the art … precision medicine to cancer patients in the VA New England system," Louis Fiore, MAVERIC executive director and POP program director, told GenomeWeb.
According to a VISN 1 spokesperson, POP, which is being funded by VISN1, officially kicked off at the end of February. So far, the regional VA healthcare system has sent out a handful of patients' samples for genomic analysis to Baltimore-based firm Personal Genome Diagnostics, a spinout of Johns Hopkins University.
Testing within POP will be provided by Personal Genome Diagnostics and Menlo Park, Calif.-based Personalis. Both firms won contracts last year to provide testing for POP, which the VA may renew on an annual basis for up to five years. Personal Genome Diagnostics will test veterans using its CancerSelect targeted panel, which analyzes somatic mutations, translocations, and copy number changes in 88 genes. Personalis will providing testing with the ACE Cancer Panel Test, after CLIA approval, the VISN 1 spokesperson said.
After testing newly diagnosed veterans with NSCLC on NGS panels, POP hopes to identify the mutations driving their cancers and report the findings to their doctors. The physicians then can use the information to prescribe patients drugs that are approved by the US Food and Drug Administration for treating tumors characterized by that particular mutation.
Providing such testing, Fiore said, will "level the playing field" by removing "disparities in the care of these lung cancer patients in terms of … variations in healthcare system practices and, to be blunt, physician knowledge and understanding of this emerging technology."
Within this regional precision medicine effort, Fiore believes, there lies an enormous opportunity to simultaneously advance knowledge about the molecular underpinnings of cancers and improve the care of veterans. "That's really what the heart of the program is," he said. To those NSCLC patients receiving genomic testing within VISN 1 as part of their clinical care, MAVERIC will also be able to offer them the chance to partake in research and, with their consent, store their medical information in a research repository and follow them longitudinally to gauge how they did on the precision treatment.
"We and others believe that when you have a research activity that is entirely siloed from the clinical world, and when you have a clinical world that is entirely siloed from research activities, then you lose opportunities for the research and clinical care ecosystem to leverage what each has to offer the other," Fiore said.
"Typically, 3 percent of healthcare dollars go to research, and 90 percent go to clinical care," he continued. "So, it's no wonder that research can't inform clinical care, because it is massively underfunded."
The POP repository will be the key to connecting clinical care for veterans with genomics research. With the information in the repository, researchers can "begin to unravel the mystery of what these different mutations mean" to the care of patients, Fiore said. MAVERIC will also ask patients if they want to make their information available to drug companies so they may be matched to studies for investigational treatments that target the molecular characteristics of their tumors.
Finally, MAVERIC will ask patients for access to any leftover biological material so researchers can run additional analyses. Researchers might ask patients for blood samples, for example, to study circulating tumor DNA, Fiore posited.
MAVERIC, which is funded by the national VA Office of Research and Development, is focused on conducting research using VA's healthcare infrastructure. For example, the group uses an electronic data capture system to receive information from veterans enrolled in clinical trials at VA hospitals throughout the country.
By storing information from consented patients in a data repository, MAVERIC is hoping to create a learning system that can improve the care of veterans with cancer. "Let's say we've accrued 5,000 patients over five years, and the 5,001st patient shows up," Fiore reflected. "Is there anything we can learn from the previous 5,000 patients that would let us take better care of the 5,001st patient?"
Typically, 3 percent of healthcare dollars go to research, and 90 percent go to clinical care. So, it's no wonder that research can't inform clinical care, because it is massively underfunded.
Such a repository, according to Fiore, is particularly useful in precision drug development efforts, which are often hindered by the difficulty of finding patients with tumors harboring these seldom-seen mutations. For example, ALK rearrangements show up in 3 percent of NSCLC tumors and ROS1 rearrangements occur in 1 percent of tumors.
"A bottleneck that drug manufacturers are facing [is] where they can't recruit enough patients with lung cancer that have a particular mutation. This would provide a way of getting around that problem," Fiore said. He noted that an important aspect of the program will be to ink partnerships with drug companies that are willing to make their experimental treatments available to POP enrollees.
The infrastructure and data elements for the POP data repository already exist and will be populated with patient information in real time as MAVERIC begins enrollment. But before starting that process, POP's research component needs to be approved by an institutional review board, which Fiore expects will happen soon.
POP is hoping to genomically test between 100 and 300 NSCLC patients in the next six months. According to VISN 1 data, approximately 1,000 lung cancer patients are diagnosed each year within the New England system. Although Fiore wouldn't provide specific dollar amounts, he estimated that genomic testing each lung cancer patient would be in the range of a few thousand dollars.
Although POP is initially focused on specific lung cancer-related gene mutations, the effort may become national in a few months, Fiore hopes. If that occurs, testing would be available for any oncologist who wants to genomically characterize a cancer patient's tumor, regardless of the tumor type. "We're not going to say it has to be NSCLC," Fiore said, noting that on a national scale, MAVERIC aims to provide a service that all VA oncologists can use for their patients.
But national expansion is dependent on the regional experience. "If the clinical program is taken up widely, we can consent those patients in our research program as well," he added. "On the other hand, if precision oncology is a bust, and the handful of drugs that are approved now for the handful of cancers is as far as it gets, then we're going to have a hard time scaling it, because docs aren't finding it useful."
Before deciding whether the VA will roll out POP nationally, MAVERIC will have to provide certain metrics from the effort in New England. For example, Fiore said that the regional program will have to show how many patients got tested, how much that cost, how many received actionable information in terms of a precision treatment strategy with an approved drug, how long they survived compared to patients who got non-targeted therapies, and what benefit there was for patients who got experimental drugs.
"The test is going to be paid for by clinical care dollars not by research dollars," Fiore said. "That pipeline of funds, roughly $2,000 per patient, plus or minus, is not going to be sustained if the clinical side of the house doesn't see what the benefit is."
Fiore acknowledged that in the end, the regional experience may not convince the powers that be that the program is worth expanding nationally, but he is hoping they will see promise in the program and continue to fund it. "We're trying to convince clinical stakeholders … [that] unless and until the clinical side of the house funds research activities, they're never going to learn whether these experimental therapies work," he said. "Researchers and clinical healthcare systems must participate and help support the research agenda."