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Veterans With Targetable Mutations in Lung Cancer Not Getting Right Rx, Study Finds

NEW YORK – A significant proportion of non-small cell lung cancer patients being evaluated through the Veterans Health Administration's National Precision Oncology Program (NPOP) are not prescribed targeted therapies for actionable variants in their tumors, new research suggests.

This gap in care suggests that more education and decision support tools are needed to help physicians prescribe drugs based on highly actionable tumor alterations, researchers said at the American Society of Clinical Oncology's virtual virtual annual meeting over the weekend.

Researchers from the Durham Veterans Affairs (VA) Health System, Durham VA Medical Center, Duke University Health System, and Duke's School of Medicine retrospectively tracked prescription records of NSCLC patients in the VA's NPOP database between mid-2015 and February 2019 and identified 115 records with sufficient genetic evidence supporting the use of targeted treatments, based on artificial intelligence evaluations and manual review. However, more than 30 percent of the patients did not receive that treatment.

Vishal Vashistha, a hematologist and oncologist affiliated with the Durham VA Medical Center and Duke University, and an investigator in NPOP, presented the data at the ASCO meeting.

Past studies have suggested anywhere from one-quarter to 45 percent of those with actionable variants in EGFR are not given targeted treatments in the frontline setting, Vashistha explained.

While it was difficult to dig into the reasons for that gap in prior analyses that were based on information in cancer databases, he and his colleagues reasoned that the integrated nature of NPOP within the VHA would make it possible to track the treatments suggested in tumor sequence reports for veterans with NSCLC and the treatments they actually received.

"We sought to assess the VA's experience with highly actionable gene variants and to identify reasons for withholding targeted treatments using individual patient data," Vashistha said.

NPOP officially launched its tumor sequencing program in 2016 and has since analyzed more than 10,000 samples from veterans with advanced solid tumors using an external vendor lab. In general, tumor sequence data generated for NPOP is being analyzed with the help of artificial intelligence tools provided by IBM Watson for Genomic. Clinicians receive sequencing results in a report that includes potential therapies based on the actionable variants found, if any, which are stratified based on the level of evidence for them.

By tapping into clinical and treatment information, clinician notes, and related information going back at least six months for more than 1,700 NSCLC patients who had their tumors sequenced through NPOP or an affiliated VA precision oncology program, the team explored some of the factors that may be holding back approved targeted treatment uptake for NSCLC patients who had what would be considered highly actionable variants in their tumors.

Among the 115 patients with actionable tumor variants in genes such as BRAF, ALK, EGFR, ERBB2, or MET, the investigators noted that 37 NSCLC patients did not get prescriptions for a targeted drug. They found that roughly two-thirds of those patients had at least stage 4 disease, while around 20 percent had stage 3A cancers.

In some cases, the team found that NSCLC patients with activating EGFR alterations in their tumors did not get targeted treatment unless they had metastatic disease. Meanwhile, some oncologists did not make note of the fact that patients had their tumors sequenced or did not record the test results, which made it difficult for the researchers to pin down prescription decisions.

"Over one half of the clinical notes of our selected patients did not mention the results of tumor DNA sequencing," Vashistha said during his presentation, though the team "frequently felt that oncologists had other common reasons for withholding targeted therapies based on the information that was available to us."

The researchers did not see any examples where targeted treatment prescriptions were rejected by the VA's Utilization Management Review Services, suggesting drug coverage was not the main factor limiting uptake.

Such findings are problematic, Vashistha explained, since one of the "foundational practices" of precision oncology assumes that doctors will administer the therapies that are known to be effective and well tolerated in cancer patients with actional tumor alternations.

Moreover, "non-small cell lung cancer is viewed as the paradigm for precision oncology," he said, noting that some 15 percent of patients with NSCLC in the US have actionable EGFR mutations in their tumors and are expected to benefit from approved tyrosine kinase inhibitors.

Consequently, Vashistha and co-authors wrote in the abstract accompanying the ASCO presentation that "further provider- and oncologist-directed educational efforts are needed, as well as implementation of health informatics systems, to provide near real-time decision support for test ordering and interpretation."