Each year, the National Comprehensive Cancer Network® (NCCN®)1 issues updated clinical practice guidelines. We all need to appreciate the amount of work and effort that each committee dedicates to keeping the guidelines aligned with evidence-based clinical practice. In the end, the quality of the data supporting diagnostics, devices, and drugs matters for providers and patients and it is critical that volunteers are willing to winnow through the ever-increasing volume of relevant literature, to provide a multi-disciplinary, expert perspective on what should be considered standard of care. While I still reserve the right to respectfully disagree with some of the specific wording that gets included in guidelines, I do appreciate the incredible effort and thought, as well as the importance, of these and other guidelines.
I am proud to now be part of Veracyte and pleased to see that in the recently updated NCCN Clinical Practice Guidelines In Oncology (NCCN Guidelines®)1 for prostate cancer, our Decipher Prostate Genomic Classifier is the only gene expression test deemed as having level 1B evidence for use in guiding patient treatment. You can read more about that here.
This level 1B evidence designation is a direct result of Veracyte’s commitment to evidence generation through fruitful collaborations with key investigators and cooperative groups. And I would be remiss if I didn’t acknowledge the incredible work on this front by Elai Davicioni , our medical director for Urology, and the dedicated laboratory and bioinformatics teams. By using best practices in prospectively-designed, retrospective analyses of randomized, phase 3 trials, the prognostic strength of the Decipher Prostate test has been clearly demonstrated and meets the Simon level 1B criteria. In aggregate, the Decipher Prostate test has been evaluated in over 75 peer-reviewed, published studies involving over 100,000 patients and including 12 randomized, phase 3 clinical trials. The NCCN Guidelines®1 now also include a table, specific for the Decipher test, on the different patient populations and clinical questions where the committee is most confident in the value Decipher brings to prostate cancer management.
Now, over a decade into my time in Industry, I understand the strong commitment it takes for companies to invest in evidence generation and, importantly, to take on big, definitive trials. I also recognize the challenges we face in the precision diagnostics marketplace given the macroeconomic trends over the past two years and the premium placed on every dollar available for investment. Veracyte’s commitment to evidence generation was an incredible draw as I considered taking on my current role. I was impressed by not just the studies that they have performed, but also the approach Veracyte uses to provide both a clinically-validated test AND global transcription for each sample tested for Decipher to facilitate further research into tumor biology.
Developing a focused test by leveraging a whole-omic approach
Like many diagnostic development projects, the initial discovery of the Decipher signature used a whole-transcriptome approach to pull in as much potentially relevant data as possible. We then used advanced machine learning to determine which genes were relevant to answering the question of whose cancer was likely to metastasize. This comprehensive approach provides the most granular view possible of the cancer’s biology, which can help make important distinctions between tumors.
However, rather than reducing the testing platform to the small set of genes comprising the signature, the Decipher test was developed and validated using the same whole-transcriptome approach. For each patient sample, whole-transcriptome data is generated and the expression from the 22 genes constituting the Decipher signature are combined to generate a score. Once the tissue workflow and informatics were locked, the test was then validated in the context of 12 randomized, phase 3 clinical trials, across multiple clinical decisions, for its association with adverse pathology, PSA recurrence, distant metastasis, metastasis-free survival, progression-free survival, and overall survival.
The whole-omic approach offers more than the clinical test
While the clinically validated Decipher score is provided to improve clinical management of patients with prostate cancer, the whole-transcriptome data provides an incredible opportunity for the research community to discover new insights upon which future diagnostics and/or management approaches may be developed. Veracyte now has whole-transcriptome data for over 200,000 prostate cancer patients along with hundreds of molecular signatures, or models, that are used to analyze this data for research purposes. This tool, which we call Decipher GRID – or Genomic Resource for Intelligent Discovery – enables us and the broader research community to glean new connections between the underlying tumor biology to help uncover a greater understanding of prostate cancer, as well as novel implications for therapeutic response.
To date, more than 100 peer-reviewed studies based on Decipher GRID findings have been published and many more have been presented at leading medical conferences. Among the more exciting findings have been that certain molecular subtypes can potentially help identify which patients will respond to specific therapies. While still in the realm of research, the most promising of these insights may in the future become clinical tests. Thus, we are working to complete a virtuous cycle: Test delivery using a comprehensive platform that also fosters research, which in turn generates data to support future test development. This is what we now call the Veracyte Diagnostics Platform.
Not just transcription anymore…
Our recent acquisition of C2i Genomics, and their whole genome sequencing (WGS)-based approach to developing minimal residual disease (MRD) tests, perfectly complements our transcriptome approach to expression-based tests. The rapid reduction in sequencing costs has created an opportunity to build specific DNA-based tests on a whole-omic platform and it’s exciting to welcome the C2i team into Veracyte. The team has already engaged with key investigators across the globe to demonstrate the clinical validity of using WGS analysis of an individual and their tumor to develop a specific and unique in silico signature that can be detected through artificial intelligence and WGS of cell-free DNA even when the tumor fraction within the circulating DNA is exceedingly low.
While we are already working feverishly with the team to bring the first MRD test using C2i’s technology to market in muscle-invasive bladder cancer, we are also excited to explore the opportunities that the WGS data may provide to the broader research community using a model similar to Decipher GRID. I am looking forward to exploring how the WGS data can help not only identify who has MRD and may be at greatest risk for cancer recurrence, but also enable further understanding of tumor biology with a hope of helping the field better determine ways to manage patients that may help reduce or eliminate their risk of dying from the disease.
We are only a few weeks post acquisition, and I am already fired up to lead Veracyte in its continued dedication to research and evidence generation across our expanded portfolio, further advancing our Veracyte Diagnostic Platform.
If you are also excited – let’s find time to talk!