VA National Precision Oncology Program

The NPOP database has been used to reannotate NGS results, such as when new drugs are approved. For example, when the first neurotrophic tropomyosin receptor kinase (NTRK) inhibitor was approved, NPOP rapidly identified all living patients with NTRK fusions and notified the health care providers of the availability a potential new treatment option for their patient. ⁷ NPOP is now building a method to allow NPOP dashboard users to similarly identify patients who have not received a corresponding drug for a user-selected LoE annotation. This will facilitate a systems approach to ensure that all patients with EGFR exon 19 deletions, for example, either have received an EGFR inhibitor or are reviewed to determine why they have not. Furthermore, the database will facilitate real-world data analysis in precision oncology. For example, prior to the recent FDA-approval of poly–(adenosine diphosphate–ribose) polymerase (PARP) inhibitors for prostate cancer, 50 veterans already had been treated with one of these agents. These data can help further inform which of the many variants of DNA damage repair genes benefit from PARP inhibitors.

Ensuring Access to Care for All Veterans

With any new medical technology comes an obligation to ensure appropriate equal access so as to not exacerbate health care disparities. Veterans enrolled in VA health care are much more likely to live in rural communities than does the US population as a whole, and there was concern that these veterans would not receive NGS testing at the same rate as urban veterans. NPOP therefore was intentional during implementation to ensure rural veterans were being offered testing. Indeed, there has been nearly equal utilization by rurality. No other disparities in NPOP utilization have been seen.

A majority of veterans who undergo testing in NPOP have at least 1 actionable gene variant reported. ⁵ However, some of these are for lower LoE off-label use of FDA-approved medications, but many are for agents available only through clinical trials. Consideration of treatments available through a clinical trial is part of standard practice for patients with advanced malignancies. NPOP data have helped identify cohorts who are eligible for clinical trials on the basis of their tumor DNA sequencing results. The National Oncology Program Office has been working closely with the VA Office of Research and Development to expand access to cancer clinical trials in VA. Veterans also can be treated on trials outside VA as medically appropriate and with local VA approval.

Conclusions

The VA NPOP is one of the largest clinical DNA sequencing programs in the nation with integrated consultation services and health informatics resources to facilitate patient care, clinical trials, and health outcomes research. The clinical services of NPOP provide cuttingedge oncology services to veterans throughout VA without exacerbating disparities and will be a national resource for research.

Acknowledgments
NPOP was made possible and implemented through the efforts of a number of people in VHA, including the national and regional leaders who supported the program’s vision and implementation, especially Michael Mayo-Smith, David Shulkin, Jennifer S. Lee, and Laurence Meyer, the leaders and staff of the Massachusetts Veterans Epidemiology Research and Information Center who piloted regional NGS testing, and especially my current and former colleagues in the VA National Oncology Program Office, without whom NPOP would not be possible. The contributions of Neil L. Spector who served as inaugural Director of Precision Oncology and Jill E. Duffy in her role as Director of Oncology Operations are particularly noteworthy.