MoIDX Open Public Meeting - June 03, 2020 - JE Part A

JOCELYN FERNANDEZ
And welcome members of the Public to Noridian’s Open Meeting for three proposed LCDs.

The proposed LCDs for today's meeting include: Breast Cancer Index (BCI) Gene Expression Test, Endopredict Breast Cancer Gene Expression Test, and Phenotypic Biomarker Detection in Circulating Tumor Cells.

The meeting will be recorded. The audio recording and written transcript will be posted on our website following today's meeting.

All lines are currently being muted by our system and will remain muted throughout the meeting. Only registered commenters will be allowed to comment during today's meeting. Anyone in attendance may submit written comments.

For our commenter, you are being allotted 10 minutes to make comments. Your line will be opened when it is your turn to speak. Make sure you are not on mute within your system, or we will not be able to hear your comments. You should be prepared to begin immediately when called upon, and we'll hear the moderator’s voice when one minute remain.

By signing in today, you are giving consent to the use of your recorded voice and your comments.

Please, be mindful of sharing any personal health information. We ask that any comments may today, also be submitted in writing.

I will now turn the meeting over to Dr. Lawrence Clark for an overview of the proposed LTD.

DR. LAURENCE CLARK
Hey Joselyn, can you hear me?

JocelyN fERENANDEZ
I can hear you, Dr. Clark yesterday. And welcome to all 34 of you that have been kind enough to call in today; and I just want to verify with Jocelyn which of our three policies will mister Nall be addressing?

He will be addressing Phenotypic Biomarker Detection.

DR. LAURENCE CLARK
Okay, DL37295. Okay, I just want to make a few brief comments and, you know, I hate starting off with an apology. What I had hoped for today was to have a breadth, a couple of breast cancer treatment experts join us. For some, some additional commentary. This is a very interesting aspect of medicine. I think in British literature, it's called Tumor Modeling. I think it's also called treatment stratification in our domestic literature.

But we have 3 policies, 3 draft policies that are all addressing the treatment of breast cancer. The first two of them basically involve invasive, early stage disease in estrogen receptor positive HER2 negative patients. They basically are both addressing early stage disease.

They, basically, in terms of the T and M classifications, are addressing the same disease. And I was hoping we could have a little discussion about the differences. They seem to be at least targeting somewhat different scope of indications. I was hoping that we would be able to go a little bit more into the decision points in terms of the use of an Adjuvant Chemotherapy.

And the extension of endocrine therapy where these may be of clinical value. I also think, as you can see, we've had a lot of activity at Noridian. I think we've been challenged by our AB lead, CMD, Dr. Oaks, to speak with our societies and to have more robust commentary on the utility of the testing.

And, we're also doing some work in wound care.

We're also doing some work in cardiovascular medicine. And I do have to say, I'd like to thank all of our societies, both the state, regional, and national contacts who are willing to review and support us in all of these endeavors. I do want to, just before I skim through the other policies, I believe mister Nalls is our only speaker today. Is that correct?

JocelyN fERENANDEZ
That's correct.

DR. LAURENCE CLARK
OK, yeah. I want to give him his time and basically just conclude my preliminary remarks with a reference to the 21st Century Cures Act, and what we are supposed to be doing.

Basically, I'm just referring to 13.2.3 in terms of clinical guidelines, consensus documents and cut and consultation, directly from the PIM... “prior to drafting and during the development of an LCD if available. The Mac shelf supplement their research with clinical guidelines, consensus documents, or consultation by experts, medical associations or other health care professionals for an advisory opinion. When applicable. When a MAC consults with an expert, they shall inform and obtain consent from the expert that their opinion may be used, disclosed publicly and clearly identified as such within the proposed or final LCD.”

And we're already and have taken this challenge to hart and are, in this sort of flurry of activity, trying to and through our impac meetings, we're trying to reach out and involve more of our societies in transparent policy development.

And so, I do apologize, again, we did have a conflict with a cancer meeting, or we would have had someone discussion of the first two policies. And, Mr. Nall, I think you are now here to discuss DL38643. Am I correct on that, sir?

Mike Nall
I believe that's the right number.

DR. LAURENCE CLARK
OK then. Why don't you take it away and thank you for being here.

Mike Nall
So, thank you again. Well, my name is Mike Nall, I'm the President, CEO of Biocept Inc, and we’re all socially distancing in the room here. And the other day, when we're on the other call, we're all socially distinct seen here. I have Dr. Veena Singh, who's our Medical Director and Head of Medical Affairs. I have Dr. Julie Mayor, who heads up our CLIA lab operations and translational chain and Corey Dunn who heads up our commercial operations, including reimbursement strategy.

So, at Biocept, we are CLIA certified and cap accredited laboratory based in San Diego. We utilize our patented and proprietary technology to develop and provide liquid biopsy testing for patients who are diagnosed with cancer.

These tests are used by physicians to make treatment decisions and are based on both circulating tumor cells or CTC, as well as circulating tumor DNA or CTDNA. We're one of the few liquid biopsy labs to offer both individual gene testing by PCR FSH, as well as panels by next gen- sequencing. So, physicians are free to order exactly what they deem is most medically necessary.

On behalf of Biocept, I want to thank MolDX for the initiative and developing this policy, and today, especially, to Noridian for the review, and allowing us to hear our comments.

We fully support the proposed coverage for detecting and circulating HER2 positive cells in patients diagnosed with breast cancer. One of the assays physicians requested most frequently by … for the detection of HER2 amplification in CTC.

The clinical… oh, and I apologize, by the way. We're right by Miramar in San Diego, and so we often get aircraft flying directly overhead. So, I'll just wait for just a second.

Think he is on his way up. The clinical utility of HER2 testing for patients diagnosed with breast cancer is well understood, and our test is marketed as a complement to the initial tissue biopsy.

This paradigm of checking biomarker status is consistent with current clinical practice and well supported by clinical data and guidelines. Based on the literature, we're requesting one additional criterion be added to the policy.

The policy currently proposes coverage when the patient's cancer has not previously been tested for HER2, or the patient has a newly metastatic cancer and the metastatic lesion has not been tested for HER2.

We recommend adding a third criterion for coverage when the patient demonstrates sensitive clinical, radiological, or pathologic disease progression as determined by their position. The addition of this criterion would facilitate coverage to repeat her to testing when clinically appropriate.

We know from the literature that breast cancer tumors have a great deal of heterogeneity and biomarker status evolves over the course of the disease. Determining the most current biomarker status for a patient is critical in order to administer the most appropriate therapy. Continuing to give ineffective therapy or conversely, depriving a patient of potential response to therapy negatively impacts patient outcomes.

And thank you all again for your consideration.

DR. LAURENCE CLARK
Mr. Nall, I'd like to ask a couple of questions and we'll give you the credit time for the flyover. Number one, you had talked about adding a third bullet. The first bullet says, the patient's cancer has not previously been tested for HER2, is that even realistic in this day and age?

Mike Nall
I think in the initial biopsy, it's probably not realistic. As you've indicated, the vast majority of patients would have that maybe in the case of bone biopsy or it's just not appropriate due to the calcification required. That could affect the expression or the amplification. But, you know, when they, very often, I think a lot of patients develop mets are not given that opportunity, just because of, maybe, their current status of care, or the physicians… Even though this has been around for what, the need to retest and the guidelines, for probably almost 10 years. A lot of patients just aren't getting it done. So, a liquid biopsy makes that possible, and very straightforward. But the third criterion that we're asking for is when a physician says, the patient's tumor is growing, or the patient's showing signs of clinical or radiologic progression or pathologic progression, and they want to make sure that they haven't missed an opportunity to put the patient on an anti HER2 therapy.

DR. LAURENCE CLARK
So that differs from bullet number two in that the disease has not completely remitted but is now progressing. Is that the difference between them? And you can ask the clinician that's accompanying you to help with this, if you want.

Mike Nall
Yes. In fact, I, I appreciate you letting me know that. When you said we can have one, I'm sure Dr. Singh would like to share a few comments. Go right ahead.

Dr. VEENA SINGH
Thank you, Dr. Mark, yes, that is correct. So, the scenario that my colleague just described is, the patient is diagnosed with primary breast cancer and has had the initial biomarker evaluation, but we do know that the septum of status changes over time not only for HER2 the ERNPR as well. So, what we're proposing is that if there’s clinical signs of progression and especially if a biopsy is not feasible for reasons such as maybe the CNS progression, for example, bony disease, visible and imaging that render, biopsies 1. not feasible 2. the results cannot be determined to be accurate because, of course, in bone biopsies because of the decalcification process, you don't know if a patient is truly negative, or its negative, because of the, you know, it's technical artifacts. So, that's the reason for us including the third criteria. Then, the signs of progression of the patient are not responding to the chosen line of treatment.

DR. LAURENCE CLARK
All right. Can I ask you another question while you're on?

Dr. VEENA SINGH
Yes, of course.

DR. LAURENCE CLARK
Ok, there is a reference, its reference number nine in the policy, that I was just wondering if you could help me understand. I've been trying to do a little of the rating. And this is, believe me, not my expertise. I am looking forward to some folks from the societies to help me with this. But there's a sentence there. Conversely, research has shown that patients with HER2 positive tissue in early breast cancer, may have HER2 negative CTCs and it is positive that this may contribute to drug resistance. Is this a common phenomenon that the tumor actually changes? And how does this compare to doing a second tissue biopsy with genotyping?

Dr. VEENA SINGH
I mean, does this have to…

DR. LAURENCE CLARK
Sorry. Go ahead.

DR. LAURENCE CLARK
I'm just asking how often that happens that the patient with HER2 positive tissue in early breast cancer has HER2 negative CTCs on a subsequent determination? And how does that impact the value of the test?

Dr. VEENA SINGH
Excellent question. Before I frame what happens between the primary tumor and the metastatic lesion on the CTC side, I just want to frame the background of breast cancer and the biology of breast cancer. In fact, there are some really nice publications in the journal from the National Cancer Institute that was published a few years ago, and it was a meta-analysis of 39 studies. And basically, what they discovered was between the primary breast tumor and paired distance metastasis to HER2 conversion rate, it converted the frequency for about 10%. It went from negative to positive in about 6% of the patients and even from positive to negative in 31% of the patients. So, we do know this is conclusive evidence in a meta-analysis of several studies have shown that the biomarker receptive status, definitely changes over time. The biology is established. Now coming back to the CTC side of things, we actually undertook a study with the Dana Farber, Cancer Institute, Verdi.

We analyzed the subset of patients who had, who were clinically HER2 negative and in 22% of these patients we found HER2 amplification, HER2 amplified on the CTC's, demonstrating the unmet need of an end to the reason for this, you know, supporting the LCD and the request to include the third category.

DR. LAURENCE CLARK
Thank you. Thank you very much, And thank you for this, very interesting. I would like you, if you'd be so kind, as to, besides introducing yourself electronically, please, put those comments in writing, along with the two references, so that we can archive it with policy. But, thank you very much for being on. Do you have anything else to add? I'm giving you extra fly over time. Do you have anything else to add?

Mike Nall
Yeah, doctor Singh would like to add one more point. Thank you.

Dr. VEENA SINGH
Thank you for giving us the extended time, Dr. Clark. The other point I just want to stress is that, you know, so we know that the biomarker receptor status changes over time, especially between the primary and metastatic tumor. We know that CTCs have been validated. In fact, in our validation, we had 93% concordance between our CTC results and tissue results. And furthermore, we know there's a discrepancy. And just most recently, there's a publication from Northwestern University and Dr. Christopher Natalie, who's a leading ... breast cancer of liquid biopsy that demonstrated an improvement in both disease progression as well as overall survival for patients in terms of the presence, or absence of HER2 amplified CTC's and subsequent therapy. So, there's also some clinical utility that has been demonstrated in this regard.

DR. LAURENCE CLARK
Thank you. Yes, I actually read some of his things in a prior, in a prior contractor role looking at some of these issues. So, thank you for bringing that. Can you refer to that article as well? And thank you very much. Jocelyn, I assume… let me just say we're going to have another meeting. How many speakers do we have for tomorrow?

Jocelyn Fernandez
Doctor Clark, I don't have that information with me.

DR. LAURENCE CLARK
Does anyone, Rachel?

I was going to say, we're going to have several additional policies, and we have a number more speakers tomorrow to discuss the policy. So, I think tomorrow should be as interesting as today. I want to thank the folks that have joined us today. I also want to say for those of you who are season ticket holders, on June 10, I will be joined by my Noridian colleague, Dr. Manuel Publliones to talk about urine drug testing. I think that's on June 10th, and as a Psychiatrist, he has significantly more personal experience with this service than I do. So, I think that it's going to be very interesting.

So, we welcome you, your participation. Jocelyn, is there anything, and I think we need to let people know the mailbox for submission of comments. And, again, thank you for joining us today, and thank you for your assistance there, Dr. Singh. Jocelyn?

Jocelyn Fernandez
Sure. Before we end, let me just move back to the first two policies. And just for the record, for the Breast Cancer Index Gene Expression Tests, there were no registered commenters. The second LCD, Endopredict Breast Cancer Gene Expression Tests, there were also no registered commenters.

DR. LAURENCE CLARK
I would add one point, then. If we would put forward for the record the two codes were DL37822 and DL37295. And what was very interesting in these policies that I would like our commenters to address, there's a reference Pritchard on the Breast Cancer Index that estimates the incidence of ER positive HER2 negative breast cancer is 80% in post-menopausal women. And in the second service, Endopredict, there's references how later and/or cell, I think, references number 3 and 4, and they estimate this same clinical and pathologic staging of cancer as 57%, which is a significant difference in the Medicare population. And I think if somebody who is able to write in and explain the difference or the difference in the cohorts or whatever, it would be appreciated. So, thank you, I didn't mean to interrupt you.

Jocelyn Fernandez
No problem. I'd like to say, in closing, we would like to communicate the next steps in the policy development process.

The comment period for the proposed LTVs will remain open until June 12, 2020. As noted earlier, all comments to be considered by our medical director for the proposed LCDs must be submitted in writing. Written comments can be e-mailed to policydraft@noridian.com, or mailed to the address on your screen. Comment information for our proposed LCDs are located on our website at Noridianmedicare.com. Upon review of the comments, our medical directors will either finalize or retire, the proposed LCDs. Please monitor our website, or register for listserv notifications to be informed of action taken on our proposed LCDs.

Doctor Clark, do you have any final comments?

DR. LAURENCE CLARK
Nothing except to thank our guests today. I really appreciate it.

Jocelyn Fernandez
All right, OK, thank you for everyone. Thank you to everyone for joining our call. This concludes our meeting and enjoy the rest of your day. Thank you.