Precision Medicine and NGS Cancer Panels — ASCO Round-Up Part Two
As we wrote in our last post, precision medicine in oncology was the big theme of this year’s ASCO meeting. One of the key advances that has made possible this focus on treating cancer based on particular biomarkers expressed by a patient’s tumors, has been the advent of Next-Generation Sequencing (NGS)-based analysis of tumor DNA. These methods have permitted the identification of specific cancer alterations and other cancer-associated cellular markers both in tumor tissue and blood, at ever increasing speed and decreasing cost.
As a result, a number of NGS test panels that screen for biomarkers associated with certain tumor types have arisen. Such test panels can help guide the treatment for a patient’s cancer, provide information on disease prognosis, match patients to potential clinical trials or point to the risk of cancer recurrence or emergence of other cancers.
Data reported at ASCO suggested that NGS test panels could result in significant savings compared to other cancer testing strategies: the use of panels rather than sequential single-gene tests to detect genomic alterations in patients with metastatic non-small cell lung cancer (NSCLC) could save the U.S. Center for Medicare and Medicaid Services (CMS) up to 2.1 million for every million patients covered, according to a cost modeling study. Moreover, NGS could theoretically lead to much faster test results compared to other testing methods in tumors like NSCLC, where testing 4-5 biomarkers is common, an important consideration for patients in need of decisions about their treatment. Indeed, the CMS has signaled in March an increased interest in NGS, by expanding its national coverage of NGS testing to FDA-approved tests for patients with relapsed, refractory or stage 3 cancers, in addition to the patients with stage IV disease previously covered.
Most NGS panels now sequence between 50 and 400 genes, and the numbers continue to rise. At ASCO, the clinical relevance of these increasingly larger NGS panels was the subject of discussion, given that only a fraction of the alterations detected can currently inform treatment decisions or indicate potential eligibility for clinical trials. And even if the findings of a particular panel point to the possibility of such a trial, the patient may not in fact be eligible because the study is too far away, their disease is too advanced, or they may simply be unwilling to participate. This raises an ethical question for doctors: Is it fair to provide hope to patients through such extensive testing, when in most cases, the patients will not be eligible or otherwise able to participate in a clinical trial?
To complicate matters further, NGS testing has been mainly restricted to centers of excellence due to lack of reimbursement and technologies being mostly too cumbersome for use in the community setting. How can we extend the reach of such testing advances and their potential benefits beyond academic centers? Doing so will likely require education about the availability and relevance of such tests, as well as the introduction of tests that are less expensive and easier to interpret. Access would also be improved by the availability of simpler testing methods that could be performed within the average clinical laboratory rather than by an outside testing service.
Ongoing studies will hopefully help answer some of the questions raised above, and steer future use of NGS testing; the National Cancer Institute Match trial in the United States is looking at overall cost-effectiveness and benefit of broad NGS testing. Bristol Myers-Squibb and Roche will also help shape the NGS landscape if they obtain approval for tumor mutation burden (TMB) testing as a companion diagnostic in NSCLC; they are investigating TMB testing using Foundation One, one of the largest NGS panels broadly available.