NEW YORK – The University of Kentucky Markey Cancer Center is evaluating how the personalized treatment recommendations of its molecular tumor board are impacting the outcomes of lung cancer patients receiving care at its community affiliate sites.
The cancer center began enrolling patients from community sites last month in a study, dubbed PRiMAL (Precision Medicine Randomized Clinical Trial Comparing Molecular Tumor Board Assisted Care to Usual Care). Researchers aim to enroll 500 patients with newly diagnosed, stage IIb-IV non-small cell lung cancer from the community sites, said Jill Kolesar, codirector of the molecular tumor board at UK's Markey Cancer Center and the principal investigator of the PRiMAL trial.
This community-focused trial is a larger follow-up to a study Kolesar's team published in 2021, looking at the impact of MTB-recommended therapies on patients seen at Markey. That earlier study suggested that patients who didn't have an MTB review had poorer survival outcomes than those who did.
"At Markey, every patient who is treated here will have a molecular tumor board review if they have next-generation sequencing performed," Kolesar noted, adding that with the PRiMAL study, her team is focusing on "getting NGS implemented more widely into the community," which then sets these patients up to have the test results reviewed by the Markey MTB.
"What we want to do with the molecular tumor board is increase the number of patients that get NGS, and if they have a mutation that's actionable, then they can get that targeted therapy," Kolesar said. "It all really starts with getting the testing done." In the trial, the community oncologists will order NGS tests from commercial labs.
Within PRiMAL, researchers are comparing two primary endpoints — one-year overall survival and quality-of-life changes — depending on whether patients received an MTB review or usual care. The researchers will also measure the extent to which MTB review changed guideline-concordant care and patients' treatment satisfaction, as well as gauge the circulating tumor DNA (ctDNA) variant allele frequency as a biomarker of response.
While the study will also enroll about 500 patients getting treated at Markey, Kolesar said the outcomes of this subset will not be included in the final impact analysis, which will be focused only on community patients' experiences. "We're an academic center, and it's not really a fair comparison because we're bigger than [community practices] are, [and] we have more specialty services," she explained.
The researchers are expecting it will take them two years to fully enroll the trial, and they'll collect data for two more years. So far, there are 60 patients enrolled mostly at Markey, and nine out of 10 community sites around Kentucky have been activated to begin accruing patients.
Outside of the PRiMAL trial, Markey has continued to improve its MTB, steadily increasing the capacity to review more cases since launching it in 2017. In 2022, the MTB reviewed more than 900 cases, 851 of which were patients from Markey and 95 from community sites. The first year the MTB was in operation, experts reviewed 211 cases, including 56 from the community affiliates.
In the early days of the MTB, Kolesar's team conducted focus groups with community oncologists to better understand their needs and realized that their colleagues in the field did not feel equipped to decide when to test patients and interpret their NGS reports. They also didn't have the time to read these often-lengthy reports or attend MTB meetings, Kolesar said.
To help busy oncologists with the time issue, Markey piloted a nurse navigator program last year to support the entire process of getting patients tested. Kolesar, who also led this program, said her team hasn't yet published on its impact but preliminary results suggest that nurse navigators have helped increase guideline-concordant testing from about 40 percent of cases to about 80 percent and decreased turnaround time from ordering the test to receiving MTB recommendations from 180 days to about three weeks.
Many studies have shown that patients who are treated with therapies recommended by an MTB tend to have better outcomes than those who don't undergo MTB review. A 2021 UK study found that patients on treatments without MTB review had more than eight times higher risk of dying than those with similar clinical features who received MTB treatment recommendations.
In another analysis of MTB outcomes from the University of California, San Diego, patients with a high match score between their tumors' molecular characteristics and the therapy recommended by the MTB had improved median progression-free survival and longer overall survival compared to those with a low match score.
Even though studies have shown that patients on MTB-recommended therapies fare better than those who don't, at present, such expert input is largely available to patients if they're getting treated at an academic cancer center like Markey or a well-resourced healthcare system. The lack of MTB access compounds existing barriers patients already face in getting on precision oncology treatments, including lack of testing or slow test turnaround time, physicians' lack of genetics knowledge, insurance coverage, and clinical trial availability.
Even at cancer centers with MTBs, patients' access to precision medicine may still be limited by these pervasive systemic barriers. For example, an analysis of a decision support program deployed for gastrointestinal cancer patients at Dana-Farber Cancer Institute showed that even though MTB case review improved precision oncology access, only a minority of patients ultimately ended up on recommended treatments due to various reasons, such as not being able to participate in trials.
Still, with studies like PRiMAL, Kolesar is interested in proving to physicians, legislators, and insurers that cancer patients are better off when they are getting guideline-concordant NGS testing and have MTBs reviewing the results to guide treatment decisions. Payors don't reimburse for MTB-review of NGS reports, although Markey provides the MTB review at no charge. While coverage for the NGS panel testing has improved for cancer patients in recent years, there are still barriers.
"It has been an uphill battle getting next-generation sequencing testing paid for. It's important for the external stakeholders — generally [commercial] insurers, Medicare, and Medicaid — to understand the value," Kolesar said, noting that focus groups have shown that not all healthcare stakeholders are convinced of the value proposition when it comes to NGS panel testing. "The more we can demonstrate the value, the easier it will be to operationalize."
To that end, Kolesar testified last month before state legislators in support of a bill that aims to establish biomarker testing coverage criteria for health benefit plans and Medicaid compliance with the requirements in Kentucky. The Kentucky House of Representatives unanimously passed the bill last month and it will be up for a vote in the Senate soon.