Nick Mulcahy

March 23, 2011

March 23, 2011 (Hollywood, Florida) — Molecular testing in cancer is "an immature industry," according to a prominent oncologist participating in a panel discussion of the testing here at the National Comprehensive Cancer Network (NCCN) 16th Annual Conference.

Dr. Mark Kris

This assessment, by Mark Kris, MD, from Memorial Sloan-Kettering Cancer Center in New York City, was echoed by other panel members. The panel participants — from government, academia, industry, and nonprofits — told tales of runaway testing, mysterious billing, underregulation, confused patients, scarce phase 3 trials, and impractical logistics.

The expert panel discussed 4 areas of testing — regulatory responsibility, data/evidence, translation into everyday practice, and value.

"We need to bring order out of chaos," said Andrew C. von Eschenbach, MD, from Samaritan Health Initiatives, referring to the regulation of molecular testing, which is a broad topic that includes tests for disease diagnosis, patient prognosis, and the prediction of therapeutic efficacy.

Dr. von Eschenbach, who is a former officer at the National Cancer Institute and the US Food and Drug Administration (FDA), believes that the FDA is the best candidate to provide the "needed [regulatory] standardization."

Currently, the FDA regulates tests that are marketed as a "kit," noted Scott Gottlieb, MD, from the American Enterprise Institute. But the Clinical Laboratory Improvement Amendments (CLIA) regulates tests that are done by labs.

Dr. Gottlieb supports having either the FDA or CLIA regulate the analytic validity of molecular testing, but prefers leaving decisions about clinical validity to the clinical community.

Dr. Gottlieb predicts that there will be a "new regulatory scheme" for molecular testing and related devices in the next 12 to 24 months. Payment will also change, he believes, because reimbursements are currently made on the basis of the number of steps involved in the test.

There is a near complete absence of level 1 evidence (from randomized controlled phase 3 trials) supporting the utility of molecular testing, said Dr. Kris, citing as an exception DNA-based KRAS testing in colorectal cancer, which is predictive of the efficacy of the targeted therapies cetuximab and panitumumab. However, despite this lack of level 1 evidence, testing for EGFR mutations is highly predictive of efficacy of targeted therapy in lung cancer, he added.

Michael Kolodziej, MD, medical director of Innovent Oncology, a division of US Oncology, and a practicing physician specializing in lung cancer in Albany, New York, said that US Oncology routinely tests lung cancer patients for the EGFR mutation. There is "good evidence" of the utility of EGFR testing, said Dr. Kolodziej. "The test should be done."

However, Dr. Kolodziej suggested that the proportion of lung cancers reported to have an EGFR mutation (10% to 15%) might be an overestimate. "I can't remember the last time I had an EGFR mutation."

We have the illusion we are in the era of personalized medicine.

In general, the practical value of testing is overblown, said Dr. Kolodziej. "We have the illusion we are in the era of personalized medicine," he explained.

Lee N. Newcomer, MD, MHA, from the UnitedHealth Group, said that lung cancer patients routinely have "180 or 190" molecular tests done, despite a "lack of evidence" of their validity.

We have to get better at analytic validity.

In addition, molecular testing is plagued by inaccurate results, said Dr. Newcomer. "Thirty percent of the HER2 tests have the wrong results," he told the NCCN audience. As a consequence, some patients are either overtreated or undertreated. "We have to get better at analytic validity," he summarized.

Dr. Newcomer also noted that the United States needs a "new system for billing for this testing." Currently, the system used to code procedures for insurance payments does not specify which molecular test is being performed. The coding just indicates "genetic test," he said.

"We don't know what we are paying for," he said. The absence of more specific coding does not allow assessment of costs or benefits that could help establish the value of individual tests, he explained.

Patients are often uncertain about molecular testing, noted Elizabeth Thompson, from Susan G. Komen for the Cure, a breast cancer advocacy organization. She said that testing is "one of the most confusing and challenging" aspects of cancer for patients. She called special attention to hotline callers who phone Komen for advice about Oncotype DX results, who say: "My test says I don't need chemo but my doctor says I do."

Practicalities Pose Hurdles

The practicalities of molecular testing were questioned by panel members. A "big issue" is getting a specimen from a pathology lab at a hospital to a molecular lab, said Dr. Kris.

Dr. Kolodziej agreed, and added that regulatory and insurance issues are part of the logistical challenge.

He told the audience about one of his patients — a female nonsmoker diagnosed with nonsmall-cell lung cancer. Because she fit the profile of patients who have tumors that might have a rearrangement of the ALK gene, and therefore might benefit from the investigational drug crizotinib (Pfizer), the woman was a candidate for genotyping of her lung tumor tissue.

In addition to having a hard time finding a commercial lab to do the test, there were "regulatory hurdles" (the state of New York restricts the types of medical tests that can be done) and insurance problems related to tests for investigational agents, Dr. Kolodziej noted.

It was a lengthy process, he told the audience, and in the end, the patient did not have the genotype suited for treatment with crizotinib.

Dr. Kris reports being a consultant to Boehringer Ingelheim GmbH, Celgene, Daiichi-Sankyo, GlaxoSmithKline, Merck, the National Cancer Institute, Novartis, Chugai Pharmaceutical, EMD Serono, and Syndax Pharmaceuticals.

National Comprehensive Cancer Network (NCCN) 16th Annual Conference. Presented March 12, 2011.

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