Somatic genomic testing should be a routine part of clinical care for many patients with metastatic or advanced solid tumors, according to a new ASCO provisional clinical opinion.1 As reported in the Journal of Clinical Oncology, the expert panel found that genomic testing in oncology practice has evolved to the point where a wide spectrum of patients with cancer may benefit. Although more research is needed, oncologists must be aware of its utility and outcomes.
Funda Meric-Bernstam, MD
“I think this guidance is extremely timely now because there has been a great interest in oncology in the past several years about the role of genomic testing (ie, for which diseases should it be performed, what kind of testing needs to be performed, and whether there is value added for genomic testing beyond diseases where there are already disease-specific, biomarker-linked therapies available),” said Funda Meric-Bernstam, MD, of The University of Texas MD Anderson Cancer Center and Expert Panel Co-Chair. “These are all areas that need to be addressed and that all oncologists should be thinking about.”
Oncologists Encouraged to Regularly Use Genomic Testing in Certain Populations
The Expert Panel reviewed the approved testing and therapy combinations, available data on marker prevalence, and expert opinions when creating the provisional clinical opinion. Although level I evidence for the utility of genomic testing is lacking, several genomic biomarker–linked therapies have already been approved by the U.S. Food and Drug Administration (FDA). The provisional clinical opinion offers a framework by which oncologists can develop a better understanding of genomic testing, its potential utility, and whether and how to incorporate it into clinical care.
Articulated within this framework is a recommendation to encourage oncologists to regularly use genomic testing for certain patient populations. “The panel felt that the time has come for genomic testing to be a routine part of the care of patients with advanced solid tumors. That can be done
Mark Robson, MD, FASCO
through multigene panel testing rather than through specific biomarkers or 1-to-1 biomarker evaluations,” said Mark Robson, MD, FASCO, of Memorial Sloan Kettering Cancer Center and Expert Panel Co-Chair. “Multigene panel testing should be part of the characterization of a patient’s tumor because even though it doesn’t always have an immediate therapeutic impact, there are enough times that it does that considering this [to be] routine is appropriate.”
He did note that somatic genomic testing does not necessarily benefit every patient. For instance, a patient with metastatic disease who has a low probability of having a genomic biomarker linked to an approved drug, and who does not have access to appropriate clinical trials, may not benefit from testing. However, it would still be useful to exclude the possibility of benefit from a pancancer treatment, such as pembrolizumab, which is approved for all patients with high tumor mutational burdens.
The provisional clinical opinion also addresses the pros and cons of using a biomarker-linked treatment when FDA approval is based on a single genomic test result. In addition, the panel highlights how oncologists should interpret such testing when alterations are linked to a certain therapy, recognizing that not all alterations are created the same.
Overcoming Barriers to Implementation
Understanding the applicability of genomic tests in oncology is complicated by the rapid evolution of this field. Thus, the panel also discusses emerging research areas of which clinicians should be aware. They include the assessment of mismatch repair–deficiency status in patients with metastatic or advanced disease who are candidates for immunotherapy, and the relevance of exon-skipping alterations in patients with non–small cell lung cancer.
“Another exciting area of therapeutic development is targeting gene fusions,” Dr. Meric-Bernstam said. “Fusion testing may have value across tumor types, but their frequency is variable by disease type. In diseases where we know fusions are common, like lung cancer, it’s important for the provider to know whether a genomic test ordered includes a fusion panel.”
Interpretation of genomic tests can also be difficult. It is important to know not only how a genomic alteration affects gene function, but also whether an alteration is known to affect drug sensitivity or resistance in that clinical scenario. Therefore, outside straightforward biomarker-linked FDA indications, clinicians must be thoughtful about the off-label use of targeted agents and, whenever possible, enroll patients in biomarker-driven clinical trials rather than pursue off-label use on their own.
But that raises another challenge: traditional mechanisms, such as randomized clinical trials, are not always useful for proving the benefit of a multifaceted assessment technique such as genomic testing. There is no single body of evidence or randomized clinical trial that can speak to the impact of genomics in oncology as a whole. Individual clinical trials that are focused on specific biomarkers and disease subsets can demonstrate value for those biomarkers in patients with those diseases—but how do oncologists know whether to test for just those biomarkers, or whether to use multigene testing, which looks at hundreds of genes at the same time and may not be helpful to a given patient now, but potentially could be useful in the future?
“The information from this [provisional clinical opinion] will obviously drive, and has already driven, a lot of discoveries in therapeutics and prognostic biomarkers,” Dr. Robson said. “We don’t have [randomized clinical trials], and that’s frozen the field in place. But hopefully this [provisional clinical opinion] will help move the field forward and bring the benefits of this technology to a wider range of patients.”
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Originally published in ASCO Daily News. © American Society of Clinical Oncology. ASCO Daily News, February 18, 2022. All rights reserved.
