New Cancer Biomarker Tests Stunted by 'Vicious Cycle'

Nick Mulcahy

August 05, 2013

Cancer biomarker test development and adoption has "lagged far behind" recent advances in cancer therapies, according to a commentary published in the July 31 issue of Science Translational Medicine.

"Despite prodigious advances in tumor biology research, few tumor biomarker tests have been adopted as standard clinical practice," write the authors, a blue ribbon panel of representatives from industry, academia, and professional organizations led by Daniel Hayes, MD, clinical director of the breast oncology program at the University of Michigan Comprehensive Cancer Center in Ann Arbor.

This is a problem for a variety of reasons, including that fact that clinicians need tools to identify the patients who will most likely benefit — or definitely not benefit — from therapies, they explain.

Without robust biomarker testing, the "promise of personalized medicine" in oncology is being jeopardized, the authors say.

The note that there is no easy answer here because the tumor biomarker test conundrum is a many-sided problem that is rooted in "undervaluation" by its stakeholders.

The "lack of reliable tests stems from a vicious cycle of undervaluation, resulting from inconsistent regulatory standards and reimbursement, as well as insufficient investment in research and development, scrutiny of biomarker publications by journals, and evidence of analytical validity and clinical utility," they explain.

Undeterred by the magnitude of the problem, Dr. Hayes and colleagues propose "ambitious" reforms that, if enacted, "should result in a virtuous cycle" of biomarker valuation.

They identify 5 causes of the vicious cycle and 5 corresponding remedial recommendations.

However, they do not acknowledge what another expert in the field has identified as a key to the shortage of tumor biomarkers and, by extension, tests.

"It has proven extremely difficult to find and validate a cancer biomarker," Eleftherios P. Diamandis, MD, PhD, professor of pathology and laboratory medicine at Mount Sinai Hospital in Toronto, previously told Medscape Medical News. In 2010, he wrote an essay on the paucity of cancer biomarkers (J Natl Cancer Inst. 2010;102:1462-1467).

Many scientists, including Nobel Prize winners in basic sciences, have embarked on a path of biomarker discovery and validation and come up empty handed, said Dr. Diamandis at the time.

Causes and Recommendations

A biomarker is a biological indicator that "objectively measures or evaluates physiological or pathophysiological processes or pharmacological responses to a therapeutic intervention," Dr. Hayes and colleagues explain.

A tumor biomarker test is used to detect and quantitate the biomarker. Tests can be used for a variety of purposes, including screening for cancers and selecting optimal therapy.

There are 2 values associated with every tumor biomarker test related to therapeutics: clinical and financial. The clinical utility is fairly simple; it "provides an indication of whether a cancer patient is likely to benefit from a given treatment," the authors write.

The financial utility is a related value. "A test has financial value if its use permits the application of expensive therapeutic strategies only in a targeted population of likely responders."

However, the American marketplace does not equally value tests and drugs, they note.

"The marketplace has recognized the value of advances in cancer care that have resulted from the discovery and development of molecularly targeted therapies but not the value of robust new tumor biomarker tests to guide patient management," they write.

The result is clear. "R&D for such tests and their adoption into standard clinical practice have lagged behind R&D and clinical use of therapeutics," they assert.

The authors believe that the entire scientific and commercial apparatus involved in biomarker testing is second rate, compared with that of drugs.

"The research, regulatory, clinical-use, and reimbursement standards are not as well defined or as rigorous as those applied to therapeutics," they write.

The authors identify 5 causes of the resulting vicious cycle of second rate operations and related recommendations that would break the cycle.

Table. The Tumor Biomarker Test Vicious Cycle: Causes and Recommendations

Cause Recommendation
Inconsistent regulatory standards for clinical data needed to approve tests Reform regulatory review of tests and ensure that "high levels of evidence" are provided, on par with that of therapeutics
Poor reimbursement levels for tests with established clinical utility Increase reimbursement for proven tests that help determine which therapies work
Insufficient investment for test development and clinical research Increase government and industry investment for test research so it is comparable to new drug research
Insufficient scrutiny by peer-reviewed journals for tumor biomarker research publications Increase the rigor for peer review
Lack of high-level evidence for tests supporting recommendations for clinical use Include only proven tests in evidence-based care guidelines


"These recommendations are not about creating more regulation; they are about creating an even playing field that allows tumor biomarker tests to be developed and proven clinically relevant. We want to stimulate innovation yet hold investigators and clinicians to the highest scientific standards — as we now do for therapeutics," Dr. Hayes said in a press statement. "We need to change the way we value tumor biomarkers in this country."

Dr. Hayes reports being a consultant for Oncimmune LLC, Inbiomotion, and Biomarker Strategies; receiving research funding from Novartis, Veridex (Johnson & Johnson), and Janssen R&D, LLC (Johnson & Johnson); being a coinventor on a patent for a method of predicting progression-free and overall survival in metastatic breast cancer patients using circulating tumor cells; and having applied for patents on a test for the diagnosis and treatment of breast cancer and for circulating tumor cell capturing techniques and devices.

Sci Transl Med. 2013;15:196cm6. Abstract


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