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Aetna Policy Bulletin Indicates Insurer Unlikely to Cover Most Proteomic Cancer Tests

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Insurer Aetna last month released a clinical policy bulletin providing an assessment of various available molecular-based cancer diagnostics and markers.

Classifying these products as either "medically necessary" or "experimental and investigational," the bulletin offers insights into how a number of molecular tests, including proteomic tests, are currently viewed by a major insurer.

For proteomic-based tests, these insights are not particularly encouraging, as all such tests are classified in the bulletin as "experimental or investigational," meaning that Aetna policies are unlikely to cover them.

In most instances, the bulletin cites insufficient peer-reviewed evidence as the reason for such classification. In the case of some tests, however, the existing evidence cited appears to leave out some recently published studies and statements. The bulletin includes, as well, evaluations of some proteomic tests that have long since been taken off the market.

With more than 22 million customers in its medical group, Aetna is one of the largest private medical insurers in the US. The company declined to comment on the bulletin.

Perhaps the most prominent proteomic test classified by Aetna as experimental and investigational is Vermillion's OVA1. In coming to this determination, the insurer cited a 2010 editorial in Obstetrics & Gynecology by Carolyn Muller, a professor in the department of obstetrics and gynecology at the University of New Mexico Cancer Center that stated that "the role of OVA1 in a generalized practice setting and cost-benefit ratio has yet to be determined."

It noted as well that the American Congress of Obstetricians and Gynecologists said in a 2011 opinion that the clinical utility of the test "is not yet established."

The Aetna assessment did not mention, however, a number of statements and peer-reviewed studies issued on OVA1 since that time. For instance, in May 2011, researchers associated with the company published two peer-reviewed papers in the journal Obstetrics & Gynecology that indicated that replacing the protein biomarker CA125 – which is classified by Aetna as medically necessary – with OVA1, increased the sensitivity of ACOG's guidelines for referring women with pelvic masses to gynecologic oncologists. Current ACOG guidelines use a combination of CA125 and other clinical measures to identify pelvic masses likely to be malignant.

Since then, three additional studies assessing the performance of OVA1 have been published in peer-reviewed journals. Also, the Society of Gynecologic Oncology in May 2013 issued a statement saying that "recent data have suggested that [OVA1], along with physician clinical assessment, may improve detection rates of malignancies among women with pelvic masses planning surgery."

The Aetna document does cite a 2013 ruling by BlueCross BlueShield's Technical Evaluation Center that, like Aetna, classified OVA1 as "experimental and investigational," meaning that the test did not meet their criteria for coverage. This ruling led to 10 BCBS plans reversing their positive coverage decisions for OVA1.

That decision, which Vermillion has said it will appeal, noted that while the peer-reviewed OVA1 studies have shown that OVA1 improves sensitivity when used with traditional clinical assessment, it reduces specificity, and, as such, "there are problems in concluding that this results in improved health outcomes."

OVA1's low specificity has long proved an issue for the test, with several clinicians citing it in past interviews with ProteoMonitor as a likely cause behind the slow uptake of the test by physicians.

The BCBS evaluation cited in the Aetna bulletin also called into question the underlying rationale behind the OVA1 test – the need to determine which ovarian masses are likely cancerous so that these patients can be referred to gynecologic oncologists for surgery.

There exists, said the BCBS report, "some uncertainty regarding the benefit of initial treatment by a gynecologic oncologist beyond the need for reoperation in some cases.”

In addition to OVA1, the Aetna bulletin also looked at Caris Life Sciences' molecular profiling test Caris Target Now, which analyzes gene and protein expression in patient tumors to identify molecularly determined treatments.

In classifying this test as experimental and investigational, Aetna said that "evidence to support the use of Caris Target Now molecular profiling is limited to a single pilot study," an effort led by Translational Genomics Research Institute researcher Daniel Van Hoff published in the Journal of Clinical Oncology in 2010.

In fact, data from a second, similar study – one in which the Caris Target Now assay was used to identify personalized therapies for breast cancer – was presented at the American Society of Clinical Oncology's 2013 annual meeting in June.

In the study, the researchers developed, via genomic and proteomic analyses, molecular profiles of tumors from 25 metastatic breast cancer sufferers, which they then used to guide treatment. In 13 of the 25 subjects, these molecularly guided therapies extended progression-free survival by more than 30 percent compared to the patient's last treatment regimen.

The Aetna bulletin also listed Biodesix's Veristrat lung cancer test among the products classified as experimental and investigational. It did not go into detail on this test, but rather grouped it with a number of other assays of which it said that "the peer-reviewed medical literature does not support these tests as having sufficient sensitivity or specificity necessary to define their clinical role."

Since launching Veristrat in 2009, Biodesix has published a number of retrospective studies on the test, and last year the firm presented at ASCO data from a prospective clinical trial of the test that it was able to identify lung cancer patients likely to respond well to treatment with Roche/Genentech's EGFR inhibitor Tarceva (erlotinib) in the second-line setting.

In interviews with ProteoMonitor, physician opinions on the meaningfulness of this trial were mixed, however, with Nathan Pennell, director of the Lung Cancer Medical Oncology Program at Cleveland Clinic saying that based on the data he would now consider ordering Veristrat for patients in his practice when warranted. Howard West, an oncologist at Seattle's Swedish Cancer Institute, said that the test had little to offer clinicians as even second-line patients identified by Veristrat as likely Tarceva responders should probably still receive chemotherapy, the current standard of care.

Aetna also classified as experimental and investigational Provista Diagnostics' BT Test, a proteomic assay for identifying breast cancer risk. "There are no published studies of the effectiveness of this test," the insurer noted. Provista relaunched under new management in 2011 and has since renamed its BT Test as DtectDx Breast. The company last year launched a prospective clinical study of the test that it hopes to complete in the next six to 12 months.

The Aetna bulletin also contains assessments of several proteomic tests no longer on the market, specifically Correlogic's OvaCheck and Laboratory Corporation of America's OvaSure. The rights to the former were purchased by Vermillion in 2011 as part of Correlogic's bankruptcy proceedings. The latter was pulled from the market in 2008 in response to letters from the US Food and Drug Administration asserting that it had not received adequate clinical validation.

The bulletin made no mention of several proteomic tests for cancer currently on the market, including Integrated Diagnostics' Xpresys Lung test, Theranostics Health's TheraLink HER Family Assay, and OncoPlexDx's various protein-based cancer tests.

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