Precision medicine in cancer care has been anticipated and talked about for years. The ability to classify a patient based on her tumor’s molecular changes and then treat her with the right targeted therapy is a concept that gives hope to the many men, women and children diagnosed with cancer. Given recent advancements, there’s good reason for this hope.
In the last year alone, we’ve witnessed the FDA approvals of several next-generation sequencing (NGS) panels (Oncomine Dx and FoundationOne CDx); celebrated the first approval of a treatment based on a biomarker (Keytruda’s MSI-H indication); seen promising new therapies advance in clinical trials (Loxo Oncology’s Larotrectinib); and, finally, watched as the CMS finalized a national coverage determination that covers diagnostic lab tests that use NGS for patients with advanced cancer. Fittingly, the theme for the 2018 American Society of Clinical Oncology (ASCO) meeting was “Delivering Discoveries: Expanding the Reach of Precision Medicine.”
While these recent advancements bring a certain level of excitement to the industry, the reality is that a limited number of cancer patients benefit from molecular profiling. On top of dealing with low detection of actionable mutations, some physicians are struggling to interpret complex test results and address patient affordability concerns. What’s getting in the way of bringing precision medicine to more cancer patients?
Are NGS-based assays all they’re cracked up to be?
At ASCO, I had the opportunity to speak with Dr. Debra Patt, a practicing oncologist at Texas Oncology and a leader in clinical cancer informatics with experience in using system innovations to enhance care delivery, about some of the challenges that oncologists face when using NGS-based tests in their practices. Here’s what I learned:
1. Actionability is critical. NGS-based tools, designed to analyze samples for multiple genetic markers at once, provide detailed biomarker information with improved accuracy. Oncologists like Dr. Patt note widespread use of NGS-based tests in the non-small cell lung cancer (NSCLC) population, where they can uncover a wide range of actionable driver mutations with associated therapy options including EGFR, ALK, ROS1 and BRAF. In fact, numerous studies demonstrate the clinical use of NGS-based tests in profiling NSCLC patients to identify actionable mutations.
There are still many mutations that aren’t actionable. Currently, the amount of genetic information that oncologists are able to collect and interpret per patient far outweighs the number of targeted therapies available. However, more therapeutic interventions are soon to gain FDA approval or are already available in clinical trial settings. For example, genomic alterations including MET, HER2, RET and NTRK have responded to targeted therapies in clinical trials. NGS also provides a method for measuring complex genomic signatures like TMB and MSI-H, which have been established as predictors of immunotherapy response.
As Dr. Patt shared, “I think that cancer patients are best treated when the decisions made between physician and patient are nestled in evidence-based care.” That approach is certainly important to remember as precision medicine continues to take shape and seep into everyday cancer care.
2. Hospitals need the right infrastructure. For patients with relapsed or recurrent cancer or evidence of metastatic disease, NGS-based assays are designed to help guide physicians to the right treatments, but sometimes that’s not how it works. In order to make NGS-based assessments more actionable, hospital systems need to build informatics platforms that can interpret the vast amounts of data that the tests generate. Physicians are often overburdened by interpreting test results and determining what actions to take based on the data that they’ve provided. There’s a great need for more sophisticated report generation in partnership with guidance on what to do with the data.
Specifically, the ability to merge patients’ genomic information with their electronic health records will play a role in helping to “nudge” physicians toward the right treatment decisions, according to Dr. Patt. Without the proper infrastructure, physicians run the risk of misinterpreting the data or using a drug when there isn’t a targeted mutation. While Dr. Patt doesn’t expect physicians to rely solely on computers to make treatment decisions, she does believe that with the volume of information provided by genomic tests, physicians will rely on informatics to provide the right menu of options. “I do think that we all perform better when the choice architecture that's put before us is selected to be preferable,” she said.
3. More guidance will help to reveal the value of NGS-based tests. In today’s landscape, the cost of a targeted therapy far outweighs the cost of a NGS-based test, yet many physicians still see the cost of an NGS-based test as a barrier to patients. CMS’s coverage decision will help, but physicians need more policies that support utilization of NGS-based tests as well. Oncologists have many questions: How do we identify the right patients to test? When is the best time to use genomic profiling with patients? With more guidance, physicians will feel more confident that the value of testing will outweigh the costs
In pre-conference coverage, Dr. Nathan A. Pennell, associate professor of medicine at Cleveland Clinic and lead author of a study presented at ASCO this year, said, “The bottom line is ultimately using [NGS] up front resulted in the fastest turnaround time, the highest percentage of patients with targetable alterations identified and, overall, the lowest cost to payers.”
Looking ahead, the possibilities seem bright for expanding genomic profiling in the fight against cancer. For example, NGS-based liquid biopsies offer the promise of much less invasive testing, which opens the door to earlier and more frequent testing. Furthermore, NGS-based platforms are already playing an important role in helping manufacturers to identify target mutations, which can help guide their R&D efforts. And finally, as more and more data is captured from NGS-based tests, it enhances our understanding of the ways in which cancer attacks the body, which means better, more tailored treatment decisions for more patients—and that’s the real promise of precision medicine.