By Arushi Agarwal, Director
In recent years, the world of oncology biomarker testing has shifted focus to a new frontier: liquid biopsy. Early adoption has been slow due to both technical and reimbursement issues, but the recent successes realized by Guardant Health may be signaling a turning point for this testing modality.
In theory, the value proposition is simple – blood samples are easier (and often safer) to collect, ship and analyze. This ease of use can also help to facilitate serial testing in order to monitor patient response to treatment, or determine whether they are having a recurrence. More importantly, in areas like cancer where tumor heterogeneity is a significant influencing factor, the idea of querying circulating DNA or even cells has an appeal to provide a more comprehensive picture of the tumor makeup. The potential impact on patient care is immense by reducing the risks associated with biopsy collection, safer and potentially more accurate tumor testing as well as a significant reduction in wait times for critical results. Recognizing these benefits, the landscape has quickly become crowded with companies interested in launching liquid biopsy-based oncology tests for multiple applications, including screening, monitoring and therapy selection.
However, as is often the case, realizing this value in reality has been a challenge in part due to technical challenges. Widespread adoption of liquid biopsy has been slow, with early traction for therapy selection but limited use elsewhere (e.g., screening and monitoring) given additional challenges in demonstrating a meaningful impact on clinical outcomes. However, even for therapy selection, tissue is still viewed as the “gold standard.”
In order to appreciate where we are in the liquid biopsy space, it is important to remember where we started – tissue-based NGS panels. NGS testing and its value in oncology has seen a harrowed history, with the concern around “too much information” cited as a major hurdle from both the payer and physician perspective. However, as the number of actionable biomarkers in lung cancer and other indications have exploded in recent years, there has been a rush to incorporate NGS testing as routine practice in both the community and academic settings in order to keep up. Most recently, we have seen the pendulum start to swing back towards more selective use of NGS as tissue sample availability and more importantly, turnaround time, have started to create challenges in using results from NGS data to make timely clinical decisions. Here enters liquid biopsy, with the goal of addressing these challenges but also a rapid realization that the sensitivity of testing on a tissue sample is challenging to recreate with blood. Given these concerns, liquid biopsy tests have primarily been relegated to one of two positions in the clinical paradigm:
- “First Pass” – as initially seen with the T790M test in lung cancer (and now with other markers) to try and reduce turnaround time where possible, but still relying on tissue as a follow-up on negative test results
- “Last Resort” – as seen with Guardant360 and other panel tests, used as an easier alternative to a tissue-based pan-tumor test to determine clinical trial eligibility or off-label drug options
Guardant’s recent collaboration with MD Anderson with the NILE (Noninvasive vs. Invasive Lung Evaluation) study is starting to change this view. More importantly, the benefits are not just limited to liquid biopsy test developers but may also start to entice Pharma to drive adoption of liquid biopsy testing as they now stand to benefit as well. There are three key areas of the study that are likely to enable this:
1. Identification of more biomarker positive patients
For Pharma, the most significant hit to the success of a targeted therapy is early attrition of the eligible patient population. The NILE study has shown that Guardant360 may actually identify more biomarker positive patients than a tissue-based test, which may in part be technology-related but is also a factor of avoiding the longstanding issue of tissue insufficiency that often prevents eligible patients from receiving biomarker testing in the first place.
2. Reduction in turnaround time
With the imminent and often rapid progression of metastatic cancer, the decision to treat often needs to be made quickly. This decision will also be influenced by patient anxiety, and the desire to receive information as well as act on it as soon as possible. Turnaround times for NGS panels have been steadily rising which often drives physicians to intervene with chemotherapy or other alternatives rather than an appropriate targeted therapy because the wait time is simply too long. In contrast, reduction in turnaround time allows patients to receive potentially life-saving drugs (often with much more benign side effects) much faster, improving overall quality of life. Pharma once again will see an expansion in the addressable market for their targeted therapies.
3. High specificity
While the specificity of liquid biopsy has not been under as significant scrutiny as the sensitivity, the study findings will naturally lead skeptics to ask the question “were the additional patients identified by Guardant truly biomarker positive?” This study suggests the answer is yes, mitigating concerns about unnecessary treatment.
On the heels of these data developments, Medicare Contractor Palmetto has now given Guardant a positive local coverage decision for the use of Guardant360 in advanced solid tumors. As part of the decision, the test will be covered for testing advanced solid tumors when tissue-based genomic analysis is not possible, making it the first liquid biopsy genomic profiling assay to receive coverage for testing multiple solid tumors (versus being indication specific). This decision is indicative of a shift away from the idea that liquid biopsy only has utility as a “First Pass” or “Last Resort”, and demonstrates a growing acceptance to using this technology as an alternative to the gold standard. As with many novel diagnostics, Guardant has struggled to reach a steady state of consistent reimbursement, which is often a barrier to adoption among clinicians. Now two potential barriers to broad use of the Guardant360 test – technology concerns and securing reimbursement – are starting to fall away.
While the value of liquid biopsy testing is clear, the technology has long struggled to find its place in the paradigm. The hope is these new data and launches of additional tests (such as Foundation Medicine’s FoundationOne Liquid assay) will be tailwinds to help drive greater comfort and adoption among clinicians over time to eventually help move liquid biopsy closer to the forefront of oncology care.
|About the Author
Arushi Agarwal joined the Health Advances team in 2011 and is a Director in the Personalized Medicine Practice. She has expertise in developing US and international commercialization strategies for companion and high-value diagnostics.
|Health Advances Capabilities in Personalized Medicine
Health Advances has been successfully advising companies on development and commercialization of Personalized Medicine diagnostics for the past decade. Our experienced multi-disciplinary team includes Ph.D. researchers, clinical pathologists, and diagnostics industry leaders working to provide innovative strategies for diagnostics and pharma companies.