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Sutter Health Exploring In-House ctDNA Testing in Effort to Expand Precision Oncology Access

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NEW YORK – Researchers at Sutter Health are weighing the costs and benefits of an in-house, liquid biopsy testing strategy in the hopes that such an approach will expand the large health system's ability to offer precision oncology treatments to cancer patients across the diverse Northern California communities it serves.

Headquartered in Sacramento, Sutter operates around two dozen acute care hospitals and 200 clinics and provides care to more than 3 million Californians. Within this sprawling network there are doctors who work for the healthcare system and community oncologists in private practice. When it comes to precision oncology, most physicians currently order molecular testing to inform treatment decisions, including tissue and ctDNA NGS panels, from their preferred commercial labs.

According to Gregory Tranah, Sutter's executive director of precision medicine, the lack of a standardized testing framework hinders the system's ability to track the extent to which molecular testing is benefiting patients, how it's impacting healthcare costs, and what access gaps exist. Based on interactions with physicians, Tranah suspects there is inconsistent adoption of molecular profiling across Sutter's system, with doctors in the larger hospitals ordering testing more frequently than those at smaller community practices.

"Just like any new technology, some people think they don't need it or just haven't had it proven to them" that molecular testing is valuable to patient care, said Tranah. "There are always going to be … physicians who say, 'I know how to treat a patient and I don't need that information.'"

However, Tranah is hoping that evidence from the studies he's working on will convince these doctors, as well as decision-makers at Sutter, that standardizing in-house ctDNA testing across the health system is not only good for patients but makes economic sense. He is conducting this research with Canexia Health, a company that is helping large and small institutions set up local testing infrastructure with the goal of expanding access to precision oncology.

Large NGS panels that most oncologists order from commercial labs, such as Foundation Medicine and Guardant Health, gauge several dozen to hundreds of genes and can cost more than $5,000. But the reports from these "comprehensive" test panels can also be hefty and time consuming for oncologists to sift through. Despite the breadth of these panels, testing still may not identify a biomarker that is obviously actionable in terms of treatment, such as an FDA-approved drug, but may point to a more investigational treatment strategy, based on scant preclinical evidence.

Brady Davis, senior VP of business development at Canexia, estimated that by bringing a test in-house, institutions can reduce testing costs down to a few hundred dollars and improve turnaround time from weeks to around a few days. Furthermore, by implementing one of Canexia's testing solutions, which includes assays for ctDNA, gene fusions, and somatic alterations, the company touts a flexible approach, in which institutions can test patients for biomarkers with the strongest evidence of actionability using a more pared down panel, and if that comes up negative, triage them to a larger panel.

"If you reduce the report down to something that's really actionable for an oncologist ... you can get [patients] on treatment faster and the better the outcomes are going to be," Davis said.

Sutter and Canexia are particularly interested in the health economics of implementing a triaged ctDNA testing model, and they have already modeled the costs of this approach. First, researchers retrospectively estimated the costs for 22 Sutter patients who received ctDNA testing from a commercial lab like Guardant Health. Then, they extrapolated these numbers to a hypothetical population of 1,000 patients to compare the cost impact if they had all received first-line testing on Guardant's Guardant360 CDx, which analyzes 74 genes, in addition to providing a 55-gene US Food and Drug Administration-approved report, or if they had been first tested with Canexia's 38-gene Follow It ctDNA test and only negative patients received the broader panel.

Assuming a $3,500 price tag for Guardant's test and $600 for Canexia's test, the researchers found that it would cost $3.5 million if all patients received the larger panel, and $1.6 million with the triaged model, resulting in a projected savings of around $1.9 million. The retrospective analysis of 22 Sutter patients who received testing on more comprehensive, commercial ctDNA panels also showed that most patients would have received identical results and treatment recommendations from the Canexia Follow It test and few would have needed to be reflexed to a larger panel, Tranah said.

Sutter is now planning a prospective side-by-side comparison of this triage strategy against large NGS panels from commercial labs on a random sampling of its advanced melanoma and lung cancer patients. "With the prospective study, we can reconfirm the financials [seen in the retrospective analysis], but we really need to show the quality for the oncologists, who are not going to sacrifice quality for cost," Davis said.

In another ongoing study, Tranah and his team are studying the efficacy of the Follow It ctDNA test as a tool for detecting recurrence in metastatic lung and melanoma patients. Typically, these patients would be monitored at various treatment intervals with CT scans, but researchers are interested in whether ctDNA testing can detect cancer recurrence earlier and identify resistance mutations that can inform subsequent treatment.

While Sutter assesses the costs and benefits of the Follow It ctDNA test in these studies, the analysis will be performed at Canexia's lab in Vancouver. If the studies demonstrate clinical utility and cost effectiveness, then Tranah will be able to make the case to those in charge of Sutter's lab and oncology services to bring this testing in-house. Sutter already does a variety of in-house molecular testing and has the necessary logistical and lab infrastructure to do ctDNA analysis, according to Davis, but before investing in setting this up, they wanted to see the value of the triage approach.

According to Tranah, Sutter may also consider bringing NGS-based tissue testing in-house, but his team decided to evaluate the value of ctDNA testing first, since it is easier to operationalize and provides a chance to implement a relatively new test that's not yet routinely ordered by most physicians. "This gives us an opportunity to offer something novel to all of our oncologists without requiring a huge cultural shift away from the current routines of sending tissue to commercial companies," Tranah explained, adding that shipping blood samples across a large region is easier than handling tissue samples.

Improving access in the community

While most organizations are still outsourcing NGS testing, health institutions are increasingly implementing local testing strategies. In a 2019 precision oncology survey of oncologists and pathologists conducted by Novartis, 83 percent said their organizations send out NGS testing to third-party labs. However, there was a 58 percent increase from 2018 to 2019 in respondents reporting they had in-house NGS testing. Faster turnaround time and better management of patients' data were among the top advantages cited for in-house NGS testing.

"The Guardants and Foundation [Medicines] of the world are definitely going to be in business. They're going to do their work as a centralized lab and there are efficiencies of scale there," Davis said. "But we think there are also going to be a lot of systems that are going to want to bring this in-house and localize it."

Improving reimbursement can be one reason. Although there is national Medicare coverage for FDA-approved or -cleared ctDNA NGS panels for advanced cancer patients, reimbursement, particularly from commercial labs, can be uncertain for large NGS panels. A lot of commercial insurance plans are covering single-gene tests or panels that gauge less than 50 genes because they find them more cost effective, Davis said. This can result in coverage denials for large NGS panels and patients can end up with bills for thousands of dollars.

If Sutter decided to bring ctDNA testing in-house, the organization would most likely also develop processes to ensure that doctors were ordering testing that met insurers' coverage criteria to reduce payment denials. Although Canexia wouldn't be involved in Sutter's billing and insurance policies, Davis said, "We can help them with the clinical validity documentation they need to see that this would have a high benefit to the system from a cost perspective."

An internal testing strategy can also help improve access to clinical trials, which are a big part of precision oncology programs but tend not to be broadly accessible within community practices where most patients get treated. With in-house testing, the institution maintains and manages patients' samples, which also bolsters an institution's ability to do research using patients' biomarker data. "That [data] is not leaving the system," Davis said. "For healthcare systems, especially those with a research component like Sutter, that is incredibly important as you're looking at advancing clinical trials, working with pharma partners who could cover the cost of treatment for patients because they want to get them in a clinical trial."

Two years ago, oncologist Zeyad Kanaan transitioned from academia to community practice in Sutter Santa Rosa, where he is working on setting up clinical trials. He described the practice, which includes five practitioners at a single location, as a "progressive organization" that supports precision oncology efforts. However, due to the pandemic, as well as cultural, staffing, and financial barriers, he has found it challenging to set up the necessary infrastructure.

The problem, Kanaan said, is that many providers in the community view clinical trials as care provided exclusively by academic centers. The additional time and labor-intensive nature of clinical trial implementation, as well as "sparse and selective" funding, further hinders community practices from partaking in drug development efforts, he noted.

But as molecular profiling to inform treatment is becoming standard practice for more tumor types, Kanaan is of the view that community practices need to understand that not just molecular testing but also clinical trials are a critical component of precision oncology. Even if trials aren't profitable, community practices "have to understand that this is not something extra you're giving patients," Kanaan said. "This is what every patient should expect." 

Precision oncology efforts at community practices would also benefit from a more local testing process, he added. Currently, patients' biopsies from his practice are sent to a pathologist in San Francisco for diagnosis and then that sample has to be sent to a commercial lab for molecular profiling, which can take several weeks. Insurance denials or insufficient tissue may further delay results. 

"Ideally, local practices would have their own NGS platform to allow for timely and high-throughput testing," said Kanaan, who expects this will happen more as sample volumes submitted for NGS testing continue to increase. That, he believes, would allow for streamlining testing for genes that are actionable for a patient's specific tumor type, decrease turnaround time, reduce insurance denials, and allow for better management of tissue specimens for testing and research.

A local approach

Outside of Sutter, Canexia is also working in its native Canada to expand access to molecular testing and precision oncology. Within Project ACTT, for example, Canexia has partnered with organizations and labs to locally collect blood samples from lung, breast, and colorectal cancer patients across Canadian provinces and analyze them for ctDNA within its lab. Within this program, launched last summer during the pandemic when many patients were delaying cancer care, including surgical biopsies, Canexia aims to provide an alternative to NGS-based tissue testing.

To date, over 30 percent of oncologists in Canada have ordered a test through the program and more than 1,500 patients from nine provinces and two territories have received ctDNA testing funded by pharma partners. Around half of the tested patients have results that point to a targeted treatment or a clinical trial based on a detected biomarker, and around 10 percent live in remote locations where they may not have easy access to this type of testing.

Canexia and its hospital and lab partners are now building infrastructure so testing can be done locally. And, as with Sutter, the company is gathering health economic data on this approach for provincial health authorities that fund healthcare and have expressed interest in the project.

According to Canexia, however, its local precision oncology approach isn't just for large health systems. It's also translatable to smaller community cancer practices. The company has partnered with the University of South Alabama, which isn't a National Cancer Institute-designated comprehensive cancer center but still wants to expand access to molecular testing to enable precision oncology in the community it serves.

Within the 100-mile radius the university services, there are small clinics in which oncologists see at most 125 patients a year, Davis estimated. While these practices don't have the ability to set up an in-house NGS panel, with Canexia's help, the University of South Alabama can serve as a local testing hub through its CLIA-certified lab. "This becomes like a nodal network … [that can] support its localized, smaller community-based cancer clinics," Davis said.

A focus on health equity

For both Canexia and Sutter, there is also a health equity element to all this. Studies continue to show that despite greater availability of FDA-approved precision oncology treatments in recent years and exponential growth within the genetic testing industry, not all cancer patients are benefiting from these advances.

In answer to a global survey in 2019, more than 61 percent of providers said that less than half their lung cancer patients were getting guidelines-backed biomarker testing. Similarly, around a third of oncologists, pathologists, and laboratory geneticists in Canada, said in a survey last year that half or more cancer patients at their institutions receive tumor profiling in time to decide first-line treatment, while 10 percent said that only 1 out of 10 patients were receiving test results in time for first-line therapy.

Although these access disparities have been recognized for years, not much has improved, in Davis' view. "If anything, the [COVID-19] pandemic has even brought us backwards a bit with delays in surgeries, testing, and treatments, not just in the US but worldwide," he said. "It's a real problem."

The ctDNA implementation research Tranah is leading, aimed at enabling cancer molecular testing across Sutter, also aligns with the health system's launch last year of the Institute for Advancing Health Equity, where Sutter has committed to researching and identifying evidence-based solutions for mitigating healthcare access inequities. The commitment is notable since Sutter serves a racially and demographically diverse population. For example, one of its network hospitals, Sutter Delta Medical Center, serves patients in Antioch, where according to the 2019 Census, around 41 percent of the residents are white, 33 percent are Hispanic, 22 percent are Black, and 12 percent are Asian.

"Our limited knowledge of cancer biology in ethnic minorities truly diminishes the potential of precision medicine in these populations," Davis said.

If the studies underway at Sutter are successful in operationalizing in-house ctDNA testing, and as a result, the health system can increase awareness of and achieve more equitable access to precision oncology, that, Davis believes, will make the health system a positive example for other organizations grappling with healthcare disparities. "We just need a good example like Sutter to prove this out in a large healthcare system," he said.

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