Why Hasn’t Genomic Testing Changed the Landscape?

“A bad tumor marker is as bad as a bad drug”
August 2012 Vol 5, No 5, Special Issue ASCO 2012 Payers' Perspective
Caroline Helwick

Chicago, IL—The “omics” revolution produced much optimism that tumor biomarker tests based on the analysis of multiple factors, sometimes thousands, would result in truly personalized cancer care. The field encompasses biologic molecules such as DNA (“genomics”), several RNAs (“transcriptomics”), proteins (“proteomics”), and metabolites (“metabolomics”). Massive amounts of data are used to produce a profile, which is incorporated into a test that could guide patient care.

But 10 years later, the promise has yet to be realized. A panel of researchers and clinicians discussed the reasons for this slow progress at ASCO 2012.

“Unfortunately, the field of tumor biomarker research has been chaotic and haphazard, leading to many published papers in the peer-reviewed literature but very few markers that truly have clinical utility or that can be recommended for routine patient care,” said Dan Hayes, MD, a scientist and breast cancer specialist at the University of Michigan.

This situation has raised 2 key issues—the use of biomarkers in the absence of solid evidence supporting their clinical utility, and a lack of biomarkers that can lead to truly personalized cancer care.

Many Markers, Few Chosen
In a recent review of the literature, researchers found >400 new genomic and other omics-based tests in transition from bench to bedside, the vast majority of which are related to cancer (Gwinn M, et al. Genet Med. 2011;13: 161-165). However, in 2012, few such tests have actually been widely adopted in the clinic, panel participants said.

According to Muin J. Khoury, MD, PhD, of the National Cancer Institute (NCI), one obstacle is “semantics.” For instance, the word “validation” means many things to many people, he said. Precise definitions are critical to any branch of science; therefore, the independent Evaluation of Genomic Appli­cations in Practice and Prevention (EGAPP) Working Group is helping to organize the field semantically. The goal of the EGAPP Initiative is to establish and test a systematic, evidence-based process for evaluating genetic tests and other applications of genomic technology in transition from research to practice, in a manner that minimizes conflicts of interest and is publicly accountable.

The EGAPP Working Group is beginning to make some recommendations. The first is to support genetic testing strategies in individuals with a new diagnosis of colorectal cancer, to reduce morbidity and mortality from Lynch syndrome in relatives. The EGAPP Working Group is also now evaluating the use of prostate cancer single-nucleotide polymorphism panels in risk assessment and screening, as well as the value of pharmacogenomic testing of tumor tissue in patients with metastatic colorectal cancer, for building decisions regarding therapy with agents targeted against the epidermal growth factor receptor.

The most uncertain factor in this field is the assurance that outcomes are improved when biomarkers are used to select patients for treatment. David Ransohoff, MD, an epidemiologist at the University of North Carolina, said the question is, “Does the biomarker discriminate; is the result trustworthy?” He noted that computational models may perform well during the discovery phase of omics-based research but frequently fail when applied to an independent specimen or data set.

But the field has not been bereft of success, Dr Ransohoff said, citing the 21-gene recurrence score (Oncotype DX) and the 70-gene signature (MammaPrint) in breast cancer. The Oncotype DX is being prospectively evaluated in the randomized MIND­ACT trial to determine whether it can guide the use of adjuvant chemotherapy in node-negative patients.

What Needs to Be Done
“It is imperative that the field take major actions to break the vicious cycle that has led to these circumstances and to do the rigorous research needed to provide proper assessments,” Dr Hayes said. “A bad tumor marker is as bad as a bad drug.”

“When these factors are recognized and incorporated into tumor biomarker studies, the dream of personalized oncologic care will be more likely to become a reality,” he said.

Ideally, to generate higher levels of evidence, investors should develop prospectively designed and conducted trials to “test the test,” the speakers said. A few such trials are occurring in breast and colorectal cancers.

Comparative effectiveness research (CER) in genomics and personalized medicine will also be valuable as payers grapple with the cost of these new tools. Between 2009 and 2012, the NCI has funded 7 groups across the country to conduct CER.

“Yes, we can have an evidence-based process for precision medicine,” Dr Khoury predicted, “but it’s not going to be cheap. It’s going to be costly.”

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