By Turna Ray
While genomically guided cancer therapy has largely been limited to patients receiving treatment at academic hospitals or large research institutions, a new effort is underway to expand access to the community care setting.
Under a partnership with GE subsidiary Clarient, Accelerate Community Oncology Research Network, an organization that runs a network of oncology research sites, is laying plans to advance genomic medicine research in the community care setting.
The organization ultimately aims to incorporate these discoveries into routine medical care at physicians’ practices and local hospitals and plans to begin a pilot version of its model by the end of the current quarter.
ACORN's mission is to support clinical trials for community oncology practices, "so we're looking to primarily do things that we think will allow patients treated in the community to get access to the best care and to support the physicians that are delivering that care," Edward Stepanski, chief operating officer at ACORN, recently told PGx Reporter.
Within the community care setting, "the coming age of personalized medicine poses a lot of challenges for everyone in terms of coming up with new processes around how that new information is obtained at the time that it is most needed to make decisions on behalf of the patients," Stepanski added.
In December, ACORN announced it was working with GE's Clarient to establish standardized testing protocols within ACORN's network of community oncology practices and hospitals. As part of this effort, ACORN will establish methods for collecting patient samples so that information about key biomarkers that might be important for cancer diagnosis and treatment will be available at the time of care.
With patients' biomarker data stored in ACORN's electronic patient medical records, a large focus of the collaboration will be on matching patients from physicians' offices and hospitals to clinical trials investigating genomically targeted drugs.
"What we've seen is that clinical trials are changing in terms of complexity, where we have to, in the case of these targeted agents, obtain biopsies after consenting the patient, have it sent off, find out if the patient has the marker that's needed based on the targeted agent, and enroll the patient in the trial if they do. If they don't, you start over," Stepanski said. "In our opinion that's not a sustainable model as there are more and more targeted agents, more and more markers that the patient might theoretically have and [therefore be able to] benefit from that targeted treatment."
ACORN operates a contract research organization and a bioinformatics platform that it plans to use in order to translate biomarker-driven research into personalized treatments.
"The goal [is to] … get as broad an array of molecular characterization performed as early in the process as we can. You see academic centers launching programs like this where they get a lot of tests run up front at the time of the initial biopsy," Stepanski reflected. At ACORN, "we are trying to create a mechanism where patients being treated in the community can benefit from the same type of approach."
The National Cancer Institute estimates that approximately 15 percent of US cancer patients are diagnosed and treated at major academic-based cancer centers, but about 85 percent receive treatment at community hospitals in or near where they reside.
"You've got the bulk of the care occurring [in the community setting], so creating the infrastructure whereby they can offer optimal care is critical," Stepanski said. "The academic hospitals cannot possibly treat all the patients that need to be treated."
Navigating the MDx Landscape
Given the project's dual aims – driving adoption of personalized medicine in clinical care in a standardized way and matching patients in the community care setting to clinical trials based on their molecular profiles – it is fitting that the organization is working with Clarient.
Acquired by GE in December, Clarient is both a centralized resource providing diagnostic technologies developed by other companies, as well as a developer and marketer of new molecular diagnostics. The company is advancing new companion tests for treatments in breast, prostate, lung, and colon cancers, leukemia, and lymphoma.
One of the company's leading products is Mammostrat, a test that gauges five biomarkers to estimate women's risk of recurrence for hormone-receptor-positive, early stage breast cancer.
Clarient's customers include pathologists, oncologists, hospitals, and biopharmaceutical companies. It provides diagnostic test reports to its customers through a web-based portal called Pathsite.
ACORN is establishing its testing protocols for personalized medicine amid an evolving regulatory environment for molecular diagnostics — for example, there may be instances where the only available test is approved by the US Food and Drug Administration, but there will also be situations where only laboratory-developed tests are available, or where both FDA-cleared tests and LDTs are available for testing a particular marker.
As such, efforts to incorporate genetic testing in the community setting could be complicated by questions about when to use an FDA-approved test or lab-developed test already available at a local hospital or cancer care center.
For example, although the FDA approved Roche/Plexxikon's personalized melanoma treatment Zelboraf alongside a companion test for gauging BRAF mutations, several hospitals that have long performed BRAF mutation testing using LDTs have balked at adopting the new, more expensive test (PGx Reporter 9/28/2011).
"FDA-cleared markers will certainly take priority when used for clinical decision making," a Clarient spokesperson told PGx Reporter. "However, alternative methodologies [need] to be explored in a research/clinical trial setting with various pharma partners."
As an example, Clarient highlighted the fact that under its partnership with ACORN, it will provide Abbott's FDA-approved test for gauging ALK mutations when patients are likely to receive Pfizer's non-small cell lung cancer drug Xalkori. The NSCLC drug and Abbott's ALK test to pick out best responders to the treatment were launched simultaneously on the market last year.
The ALK marker "is a perfect example of where we are using the FDA-cleared test to make clinical decisions, but Clarient has a number of other methodologies to evaluate ALK alterations that could be used in a research setting," the Clarient spokesperson said.
ACORN will employ an expert panel to decide on the biomarkers that will be incorporated in the clinical diagnosis and research setting for patients treated at hospitals and practices within ACORN's network.
According to Stepanski, the panel of markers that will be incorporated into clinical care will be those for which there is already evidence in the literature as being useful in patient care. The Clarient spokesperson added that markers explored in the research setting will focus on those with the potential to become targets in drug development and that are likely to be developed into companion tests at some point.
"I ultimately think it'll be important that we know if we have 50 patients with a PI3K mutation [associated with] first-line treatment of non-small cell lung cancer, and if there is a targeted agent for that mutation in second-line therapy, that we can direct patients to that protocol," Stepanski noted. "Whether this is a protocol we would support or if it's a protocol [adopted] at some place in [our] community, we would figure that out. I imagine it would be both."
The FDA is currently establishing regulations for when certain diagnostics and diagnostic components can be used to make treatment decisions and when they can only be used in the research setting. In a draft guidance on the development and marketing of research-use-only and investigational-use-only in vitro diagnostics, the FDA outlines the appropriate and inappropriate use, labeling, manufacturing requirements, and marketing of IVDs for research and investigational purposes. FDA's overarching stance in that guidance is that products that manufacturers label as RUO or IUO, which in most cases haven't been approved or cleared by the FDA as medical devices, should only be used in research and not for clinical diagnosis of patients (PGx Reporter 6/8/2011).
So, when incorporating molecular testing into clinical care and research programs, ACORN will also need to have protocols in place for when an IUO test can be used and when an FDA-approved test should be used.
"That's what we're trying to work through. You kind of have to go marker by marker. We're focusing on markers initially where there is pretty good evidence that even if they are not listed as standard of care, there are credible, published data that suggest that this is an important marker in the context of that tumor type, and that there would be prognostic information that would inform clinical decisions on that basis," Stepanski said. "The second stage would be those markers that would be considered research only … [That part of the] program we haven't elucidated yet."
For molecular diagnostics to be implemented as part of personalized cancer care, and before clinical trial matching procedures can be established across ACORN's network, additional health IT improvements will be necessary.
Although many patients treated by ACORN network organizations have EMRs, these systems may not be structured to hold biomarker data from routine testing. "There is a lot of development that needs to be done, so we can create a pathway whereby the markers can be obtained in the most efficient manner for practices and for patients, [and] get the information back in the hands of the physicians who are going to be making decisions in an optimized way," Stepanski said. "Many of the EMRs currently being used [don't have] standard places to [enter] information on these markers. We may be looking at novel ways of getting the data and provide it back to practices in a way that's useful to them and allows them to have that information at their fingertips when they need to have it."
ACORN expects to roll out a pilot version of this community-based personalized medicine program in the first quarter of 2012. The pilot will most likely be launched in the West Clinic Cancer Center in Memphis, Tenn. According to the clinic's website, it is currently participating in more than 40 clinical trials for new drugs and drug treatments. In 2010, the West Clinic was among the few community cancer practices to receive the Clinical Trial Participation Award from the American Society of Clinical Oncology.
"After we test the processes in a beta format and fine-tune that, we'll roll it out into additional practices in our network by the second quarter," Stepanski said.
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