Local Coverage Article Response to Comments

Response to Comments: MolDX: EndoPredict® Breast Cancer Gene Expression Test

A55794

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Article ID
A55794
Article Title
Response to Comments: MolDX: EndoPredict® Breast Cancer Gene Expression Test
Article Type
Response to Comments
Original Effective Date
01/30/2018
Retirement Date
N/A
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The comment period for the MolDX: EndoPredict® Breast Cancer Gene Expression Test (LCD) L37311 began on 06/01/2017 and ended on 08/14/2017. Comments were received from the provider community. The notice period begins on 12/14/2017 and ends 01/29/2018. The LCD becomes final on 01/30/2018.

Response To Comments

NumberCommentResponse
1

Myriad Genetic Laboratories, Inc. appreciates the opportunity to comment on Draft Local Coverage Determination (LCD) MolDX: EndoPredict Breast Cancer Gene Expression Test (DL37311). We are writing to express our support for the content of the Draft LCD and to reiterate the importance of the proposed coverage for women with breast cancer.

As described in the Draft LCD, determining which patients with ER+/Her2- breast cancer will have a low enough risk of distant recurrence after 5 years of endocrine therapy to forgo adjuvant chemotherapy is a priority for physicians who manage these patients. The Endopredict 12 gene molecular score is combined with clinicopathologic features (tumor size and lymph node status) to produce the EndoPredict (EPclin) score, which is reported as low- or high-risk and includes a personalized risk of 10-year distant recurrence (DR) based on each patient’s result. 

The prognostic ability of EndoPredict has been validated by prospectively designed-retrospective studies in three different cohorts from phase III trials involving more than 2,600 patients.¹,²  These studies collectively demonstrate the ability of EndoPredict to predict the primary endpoint of DR in both early and late time periods, to accurately classify patients into a low or high risk group, and to identify a low risk group with excellent 10 year outcomes after treatment with 5 years of endocrine therapy only. 

Among patients in the validation studies:  

  • 73-78% of node-negative patients fell into the Endopredict ‘low-risk’ category with 10-year risk of distant recurrence of 5-5.9%, compared to 16-20% for the ‘high-risk’ patients.

  • 19-30% of node-positive patients fell into the Endopredict ‘low-risk’ category with 10-year risk of distant recurrence of 5-5.2%, compared to 28-36.9% for the ‘high risk’ patients.

In summary, Endopredict is a second-generation test for highly accurate assessment of 10-year risk of distant recurrence. Coverage of Endopredict for Medicare beneficiaries meeting the criteria outlined in the Draft LCD provides the opportunity for physicians to identify those patients with a low-risk EPClin score, for whom the absolute benefit of adjuvant chemotherapy is unlikely to outweigh the risks. 

 

Comment acknowledged.

 

2

On behalf of the NanoString Inc., I respectfully ask Noridian Healthcare Solutions to consider the following comments related to the recent Draft MolDX LCD: EndoPredict Breast Cancer Gene Expression Test (DL 37295). The published draft contains a misleading cross-trial comparison with the Prosigna Breast Cancer Gene Signature Assay and other minor inaccuracies. While we respectfully acknowledge the evidence evaluation performed by Palmetto, we assert that the presentation of the information in this manner may create confusion in the interpretation of comparative information between genomic tests for hormone receptor-positive early stage breast cancer for the following reasons:  

  1. In the table comparing Myriad’s EndoPredict test with Prosigna, the comparative information is derived from different clinical trial cohorts (TransATAC for EndoPredict and ABCSG.8 for Prosigna). This is an inappropriate comparison due to the differences in clinical and pathological characteristics of the patients within each cohort which produces differing risk group distributions and group estimates of survival. The presentation of this information in the table creates an impression that the results are representative of those that would be observed if utilizing the tests on an identical set of patients. The table could be construed as encouraging the inappropriate comparison as it includes a comparison of two tests within the same cohort (EndoPredict and OncotypeDX) with Prosigna which was tested in a separate cohort.  

  2. The risk score cutoff value to define the low risk group for reporting survival and percentage of patients for Prosigna in node-positive (1-3 positive nodes) patients in the table is not the same as the cutoff value utilized by the FDA-cleared product in the United States. The low risk cutoff value for node-positive patients in the United States is 40 ROR score units. The values in the table do not reflect the results that would be obtained in the United States on those same patients.  

We respectfully request removal of the information regarding Prosigna from the table in the Draft MolDX LCD: EndoPredict Breast Cancer Gene Expression Test (DL 37295) based on the points stated above. If Noridian Healthcare Solutions determines that it is necessary to include Prosigna in the table, we would like to respectfully request the following changes be made to the table in order to provide accurate information consistent with the FDA 510(k)-cleared package insert:

1. Under the ‘Low Risk Scores’ heading, the value for ‘% of Node-pos pts with Low Risk Score’ should be changed to 41.4%. The draft LCD indicated a value 4.1% which is associated with the European product labeling (CE mark).  

2. Under the ‘DR in Pts with Low Risk Score’ heading, the value for ‘Node-pos, Low Risk Score- 10yr DR risk’ should be changed to 5.8% (2.8-11.9%). The draft LCD indicated a value of 0% (0-21.8%), which is associated with the European product labeling (CE mark).  

3. Under the ‘High/Non-Low Risk Scores’ heading, the value for ‘% of Node-neg pts with High/Non-Low Risk Score’ should be changed to 53.5%. The draft LCD separates this field into two separate fields for Prosigna (Int and High), which is inconsistent with the reporting convention for the other tests. Removal of the ‘Int and High’ values and replacement with a single value of 53.5% reflects a fair comparison between the tests.  

4. Under the ‘High/Non-Low Risk Scores’ heading, the value for ‘% of Node-pos pts with Non-Low Risk Score’ should be changed to 58.6%. The draft LCD separates this field into two separate fields for Prosigna (Int and High), which is inconsistent with the reporting convention for the other tests. Removal of the ‘Int and High’ values and replacement with a single value of 58.6% reflects a fair comparison between the tests and the appropriate risk cutoffs for US patients.  

5. Under the ‘DR in Pts with High/Non-Low Risk Score’ heading, the value for ‘Node-pos, Non-Low Risk Score- 10yr DR risk’ should be changed to 24.2% (18.6–31.1%). The draft LCD separates this field into two separate fields for Prosigna (Int and High), which is inconsistent with the reporting convention for the other tests. Removal of the ‘Int and High’ values and replacement with a single value of 24.2% (18.6–31.1%) reflects a fair comparison between the tests and the appropriate risk cutoffs for US patients. 

6. Under the ‘DR in Pts with High/Non-Low Risk Score’ heading, the value for ‘% of Patients in Intermediate Risk Group’ should be changed to 23.4%. The draft LCD indicated a value of 33.5% which is associated with the European product labeling (CE mark).  

 

In summary, we are primarily seeking removal of Prosigna from the table in the Draft MolDX LCD: EndoPredict Breast Cancer Gene Expression Test (DL 37295) as it inappropriately compares results between trial populations with differing patient characteristics. Alternatively, at a minimum, we request an update to the Prosigna portion of the table to be consistent with the US product labeling cleared for marketing during FDA 510(k) review.

 

The table has been removed. 

3

EndoPredict for breast cancer – Discussed with our breast medical oncologist and fellowship trained breast surgeon, Dr. [REDACTED]. We do NOT plan to use this either. It’s a European test that has limited data and won’t supplant Oncotype Dx (for breast).

Comment acknowledged. 

 

4

I am a medical oncologist with the [REDACTED] with an interest in breast cancer. I have been with the [REDACTED] since July 1985. I have been asked to leave a comment related to my experience using this test in my clinical practice.  

So far I have used this test as a “tie breaker” in patients with an intermediate risk Oncotype DX report. I have had four EndoPredict studies done on my patients. So far these results have been helpful in giving direction to patients with regard to the need for chemotherapy. I like that it is binary with no intermediate risk group reporting.  

I have confidence in Myriad Genetic Laboratories.  I have worked with Myriad for many years for BRCA testing.  I have found the customer service to be excellent along with exceptional patient education materials.

EndoPredict was never developed to be a “tie breaker”.  Confirmatory testing (which this provider describes) is NOT a Medicare benefit. 

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