Two Trials of Note from Latest Next Generation Sequencing National Coverage Determination

The next wave of oncology testing may have gotten another boost in late January with a new decision memo from the Centers for Medicare and Medicaid Services (CMS) for national coverage for precision medicine diagnostic testing for inherited (germline) ovarian or breast cancer 

Uncertainty about coverage of precision medicine diagnostic testing is one of the major hurdles faced by hospital and health system leaders who are considering initiating or accelerating a personalized medicine program. But they received welcome news in late January when the Centers for Medicare and Medicaid Services (CMS) announced that it is expanding coverage of laboratory diagnostic tests that employ next generation sequencing (NGS) for patients with inherited (i.e., germline) ovarian or breast cancer.

CMS arrived at the decision after reviewing 24 clinical trials, all of which are summarized in the decision summary. In particular, two studies from the ARIEL2 trial--from Lin and colleagues and Swisher and colleagues--helped CMS determine that NGS would be a valuable diagnostic tool for ovarian cancer, providing "evidence of moderate quality" for its use.

For breast cancer, the evidence was also moderate, coming from two trials. Kotoula and colleagues concluded from their study of 196 women with triple negative breast cancer (TNBC) that germline and tumor genotyping was necessary to classify the disease. Their conclusion is based on an observed prognostic interaction between germline BRCA1 and TP53 mutation status. Meanwhile, Toomey and colleagues used NGS to identify ERBB-family single nucleotide polymorphisms (SNPs) that occurred in two or more individuals among patients with HER2-positive breast cancer.

The recent decision memo adds potential momentum to the use of precision medicine in oncology, which some say "is set to balloon" in the near term, according to a recent article published by the American Association for Clinical Chemistry.

Consider Patient Need and Patient Volume

Among the many factors for hospitals to consider with implementing NGS, including startup costs, recruiting research-experience medical technologists, and assembling a qualified bioinformatics team, the AACC article states, is that in many cases a facility's decision to take on in-house NGS will rest on patient need and patient volume.

In consideration of breast or ovarian cancer specifically, CMS' decision summary states that NGS is "reasonable and necessary" and, thus, covered nationally when performed in a CLIA-certified laboratory and ordered by a treating physician for patients who have:

  • ovarian or breast cancer; and
  • a clinical indication for germline (inherited) testing for those hereditary cancers; and
  • a risk factor for germline (inherited) breast or ovarian cancer; and
  • not been previously tested with the same germline test using NGS for the same germline genetic content.

Additionally, the diagnostic laboratory test using NGS must be approved by the US Food & Drug Administration (FDA), and results must be provided to the treating physician using a specified report template that outlines treatment options.

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Centers for Medicare and Medicaid Services (CMS) Administrator Seema Verma (above) now says that NGS testing provides clinically valuable information to guide patients and physicians in developing a personalized treatment plan. (Photo source: US Department of Health and Human Services)

Not All the News Was Good in the CMS January 2020 Decision Memo

Since many labs offer NGS as a laboratory developed test that does not require FDA approval, some stakeholders are worried about CMS' requirements that the covered NGS test must be FDA-approved, according to Epstein Becker and Green, a health care law firm. Indeed, this concern was voiced during the comment period after CMS proposed the change. However, according to CMS, only "tests that are FDA approved or cleared are able to demonstrate analytic and clinical validity. CMS believes that a lab developed test, even with CLIA certification, may not have sufficient evidence to demonstrate clinical utility."

During the comment period, stakeholders asked about germline testing for other cancers. CMS has decided to leave that decision up to Medicare Administrative Contractors (MACs). CMS acknowledged that "innovation is happening quickly and evidence is moving fast." Thus, it wants to "ensure that patients have ready access to this diagnostic test when appropriate.

NCD Still Only Applicable to Certain Diagnostic Laboratory Tests

It should be noted that "this National Coverage Determination (NCD) is only applicable to diagnostic lab tests using NGS for somatic (acquired) and germline (inherited) cancer," according to CMS. And "this NCD reconsideration addresses the use of NGS in patients at risk for germline (inherited) mutations and does not negate coverage of somatic testing using NGS for beneficiaries with recurrent, relapsed, refractory, metastatic, and/or advanced stage III or IV cancer."

With regard to removing the staging criteria from the original NCD for NGS, said CMS, all stages of cancer are coverable for germline (inherited) cancers. "If there is new evidence available showing patients with somatic cancers other than advanced stages benefit from NGS, CMS would be interested in reviewing those studies in a separate reconsideration."

-Dean Celia

Related Information:

CMS Expands Coverage of Next Generation Sequencing as a Diagnostic Tool for Patients with Breast and Ovarian Cancer

Decision Memo for Next Generation Sequencing for Medicare Beneficiaries with Advanced Cancer

BRCA Reversion Mutations in Circulating Tumor DNA Predict Primary and Acquired Resistance to the PARP Inhibitor Rucaparib in High-Grade Ovarian Carcinoma

Rucaparib in relapsed, platinum-sensitive high-grade ovarian carcinoma (ARIEL2 Part 1): An international, multicentre, open-label, phase 2 trial

The fate of BRCA1-related germline mutations in triple-negative breast tumors

The impact of ERBB-family germline single nucleotide polymorphisms on survival response to adjuvant trastuzumab treatment in HER2-positive breast cancer

Medicare Expands Access to Genetic Diagnostic Tests for Certain Ovarian and Breast Cancers

Dive Into Precision Medicine