NEW YORK – An analysis by health technology firm Diaceutics and the Personalized Medicine Coalition (PMC) has found that nearly two-thirds of non-small cell lung cancer patients lose out on the chance to get precision oncology therapies due to systemic failures in providing biomarker testing and matching patients to drugs based on the results.
The study, published earlier this month in JCO Precision Oncology, identified seven "practice gaps" along the care pathway that are hindering approximately 64 percent of potentially eligible patients with advanced NSCLC to lose out on receiving precision oncology therapies.
Researchers used UK-headquartered Diaceutics' Data Repository resource, Medicare claims, and laboratory data from over 500,000 NSCLC patients in the US and found that 49.7 percent of those eligible for precision therapies miss out due to factors related to biomarker testing, including issues with procuring tumor biopsies, insufficiency of the tumor sample, and failure to apply test results to guide treatment decisions.
The latest research is part of Diaceutics' ongoing efforts to understand and quantify how access disparities in precision oncology are impacting patients. For example, in 2017, Diaceutics reported that testing inefficiencies led to an estimated $8.3 billion in lost annual drug revenue within the US.
With this latest research, Diaceutics and PMC provided more granular insights into the specific points in a patients' journey where access failures are occurring. At the beginning of the diagnostic journey, 6.6 percent of patients never had a tumor biopsy performed. About 14 percent of patients were lost to biomarker testing due to insufficient tissue or tumor cell content collected from the biopsy. Another 1.7 percent of patients had tumor cell content that was overestimated, which meant the biospecimen did not meet the requirements for testing platforms and impacted test accuracy.
Moreover, an estimated 17.5 percent of patients never had any biomarker test ordered. For another 14.5 percent of patients who did get tested, the results were inconclusive or they received a false-negative result. Turnaround time for biomarker test results also led to 4 percent of patients beginning a treatment before the results were returned. Among the patients who did receive results from a biomarker test, 29.2 percent failed to receive the appropriate targeted treatments.
Susanne Munksted, senior author of the study and chief precision officer at Diaceutics, said the results should be a "call to action" for the healthcare community to come together and address these gaps. "We are not going to close these gaps or improve on the ecosystem [without] a multi-stakeholder approach," she said.
Some access gaps identified in the Diaceutics/PMC paper are easily explained, like having insufficient tissue for biomarker testing or long turnaround times for results. Others are more difficult to pin down. The proportion of patients who don't get biomarker testing at all or those who get results but aren't matched to a treatment may point to a lack of oncologist awareness of biomarker testing and new targeted therapy treatments, Munksted said.
How biomarker test results are reported, for example, can also impact the communication between labs and physicians, Munksted said. Reports, she explained, are not worded in ways that are logical to attending physicians and don't clearly explain how the results might be therapeutically actionable. This is especially true for new and emerging biomarkers.
"It will come down to lack of awareness and a lack of knowing the clinical utility" of biomarker testing, Munksted said. "It's one thing to be aware of the right biomarkers available, and then you have to act on it. You need to understand the clinical utility and understand how the results can guide the treatment."
In practice, many clinics and hospitals, especially in the community setting, still struggle with integrating precision medicine testing and treatment paradigms into their workflows.
On top of the pressure of staying up to date on the latest research, oncologists also have to manage tissue collection to facilitate biomarker testing and contend with timely test result turnaround, said Howard McLeod, executive clinical director of precision health at Intermountain Healthcare. "The idea of doing appropriate molecular testing for tumors is clear in everyone's mind, but the practicalities are still being worked through," said McLeod, who was not involved in the Diaceutics/PMC study.
He noted that some oncologists choose to look at the "old-fashioned" cancer treatment options before trying biomarker-guided treatments, while others will make decisions without waiting for all the results to come in. Some clinics may run rapid turnaround single-gene tests and make treatment decisions before results from larger next-generation sequencing panels are available.
"Psychologically, we think we would rather have information sooner than later. Part of it is impatience," McLeod said. "Oncologists would rather have some data with a more rapid turnaround, not realizing that it's insufficient data. It's just learning that the data that you get quickly is not complete data and you can't make a good decision about patient management by only getting hotspot type testing."
At a very basic level, where patients are treated — at a community practice or a large cancer center — may also play into their chances of getting precision oncology treatments. "In the communication and education [about precision medicine], there is a tendency to focus on the bigger labs and the bigger institutions, and that will potentially leave a gap in the smaller community hospitals," Munksted explained.
Laura Greco, a lung cancer patient advocate and a patient herself, understands all too well that care varies based on where someone is treated. She travels more than three hours to a large academic cancer center to get treated for ALK-positive lung cancer.
Oncologists who may not fully understand biomarker testing or explain the need for testing or the testing process, can create more stress for patients, she said. "There isn't a lot of education from the doctors as to what the process is or how long it takes," Greco said, noting that it's not uncommon for results of PD-L1 testing, which helps guide immunotherapy decisions, to be ready before NGS panel testing yields information about any targeted treatments patients may have matched to.
"That is a psychological burden for patients because they get this negative result for PD-L1, and they don't realize there's a whole list of other biomarkers they might be a candidate for," she said. "They will see this one negative, and some don't know there are other options."
According to Daryl Pritchard, PMC's senior VP of science policy, the advocacy organization commissioned a project with the Fred Hutchinson Cancer Research Center in 2019 to examine the cost-effectiveness of genomic testing for cancer patients. Through that effort, the PMC "recognized the problem that many cancer patients who were eligible for more effective personalized medicine-targeted therapies were not getting them due to clinical delivery practices gaps," Pritchard said.
Based on insights from that work and this latest research, Diaceutics and PMC are working on strategies to mitigate those gaps through efforts that include educating patients, providers, and insurers on the effective implementation of precision therapies and advocating for policies and practices that can improve efficiencies at steps such as sample processing.
For its part, Diaceutics tries to streamline the multidisciplinary communication needed to manage precision medicine cases through its DxRx platform, which was launched in 2020 and aims to connect pharmaceutical companies, companion diagnostic test developers, and the laboratories developing and performing tests. The platform also allows Diaceutics to gather data on the economic impacts of patients missing out on treatment and explore cross-stakeholder initiatives designed to bring attention to specific gaps.
"We hope to more efficiently support the management of testing in a systematic way with our DxRx platform and help the community understand that you need to focus on the entire diagnostic pathway," Munksted said. She suggested that more investment and education efforts are needed to promote wider biomarker test adoption rather than promote uptake of drugs.
Now that this study has highlighted that a significant proportion of patients miss out on precision oncology care and treatments, the next step is more qualitative research to better characterize the causes of these gaps, such as research that surveys physicians about the barriers they face, Munksted said.
The partnership with PMC will also help bring the drug and diagnostic industries together to help address these issues, she added. PMC and Diaceutics created a steering committee consisting of representatives from diagnostics, pharma, the lab industry, patient organizations, and payors to begin work that might address the gaps identified in the study.
From a health system perspective, wider use of molecular tumor boards may help address some of the issues that lead to patient loss along the way, suggested McLeod, who also is managing director at Clarified Precision Medicine, a firm that provides on-demand precision oncology expertise to oncologists who need help applying the results of genomics tests to their patients' care.
"One thing we're seeing growing is the use of molecular tumor boards, certainly within academic institutions or large health systems like Intermountain, but we're also seeing commercial availability of these [MTBs] as well," he said. "What that brings is a place to discuss what tests should be ordered with experts. In the absence of that expertise, people are ordering whatever panels they want, not realizing that there's a difference."
Greco, the patient advocate, said public and patient awareness programs about cancer biomarker testing are important, but increasing doctors' education is what's really needed amid fast-changing biomarker research and particularly among community oncologists who treat a wider range of tumor types.
"You can't put it on the patient when they're just diagnosed to try to understand the full range of treatments out there; that's not reasonable," Greco said. "What is reasonable is to expect the doctors to know they need to do NGS testing 100 percent of the time. They need to understand what NGS testing can and cannot give them. They need to understand, too, that perhaps an inconclusive biopsy result and not enough tissue is only the beginning of the story, not the end."