In the past several years, an increasing number of gene panel tests have become available for use in the clinic. At the recent annual meeting of the American Society of Clinical Oncology (ASCO), speakers discussed some of the controversies and clinical dilemmas surrounding these tests.
Mark Robson, MD, clinical director of the Clinical Genetics Service at Memorial Sloan Kettering Cancer Center in New York City, described gene panels as incredibly powerful and potentially disruptive tools. One of the biggest controversies is when to use a multigene test for cancer susceptibility.
\\\"We don\\\'t have a standard way of deciding when these types of technologies should become standard of care,\\\" said Dr Robson. He pointed out that there is a standard, rigorous way that new drugs are evaluated and adopted into practice. Drugs go through phase 1, phase 2, and phase 3 clinical trials and are then approved by the US Food and Drug Administration (FDA). \\\"Clinical adoption of the drug follows and then, generally, there is a standard of care developed through a consensus process,\\\" said Dr Robson. \\\"We don\\\'t have anything like this [process] for devices.\\\"
Gene panel tests, similar to radiographic scans, are classified by the FDA as devices. The FDA evaluates devices, but not from an efficacy standpoint. \\\"When you think of genomic testing and germline testing, there is no agency like the FDA saying, \\\'Yes, this device does what it says it does,\\\'\\\" said Dr Robson. \\\"Things move to clinical adoption through an organic process, and then a similar organic process takes place to make them standard of care. The evolution toward standard of care is not usually driven by some sort of consensus mechanism.\\\"
The Centers for Disease Control and Prevention\\\'s Office of Public Health Genomics has established a process for evaluating scientific data on emerging genetic tests, called ACCE.[1] ACCE takes its name from the four main criteria for evaluating a genetic test: analytic validity; clinical validity; clinical utility; and associated ethical, legal, and social implications.[2] Analytic validity is how well a test measures the property or characteristics it is intended to measure. Clinical validity is the accuracy of a test in diagnosing or predicting the risk for a health condition. Clinical utility is the usefulness and added value that a test brings to patient management.
\\\"Value is part of the clinical utility equation,\\\" said Dr Robson. \\\"You have to think about how much you are paying in terms of toxicity or economically to make a decision about whether something has enough clinical utility to move into standard of care.\\\"
Actionability is another term that is bandied about when discussing genetic testing. \\\"There is no universally accepted definition, but one suggestion is that an actionable finding is one that could plausibly lead to a specific medical recommendation or intervention, but there is no implication that the action is going to be beneficial,\\\" said Dr Robson.
There is a slew of data showing that clinicians change their practice based upon results of genetic testing. A recent study showed that Oncotype DX® and MammaPrint® influenced a change in treatment recommendations in 21%-74% of patients with breast cancer.[3] Retrospective analyses of the National Surgical Adjuvant Breast and Bowel Project B20 and Southwest Oncology Group SWOG-8814 trials revealed a large benefit of chemotherapy in patients with estrogen receptor–positive tumors and high Oncotype DX Recurrence Score (RS ≥ 31).[4] In another study of women testing negative for BRCA1/2 mutations, multigene sequencing identified 16 potentially pathogenic mutations in other genes, of which 15 prompted consideration of a change in care, enabling early detection of a precancerous colon polyp.[5] While it\\\'s clear that genetic tests are influencing treatment decisions, there are no prospective, randomized trials demonstrating that the changes improve outcomes.
