Early Detection, Part 2: Screening for Over 50 Cancers with Cancerguard

Chuck: Welcome to the Good News About Cancer. I'm Dr. Chuck Ryan.

In each episode of this show, we talk to one of our colleagues about a promising development in cancer. We'll break down what's new, why it matters, and how it points the way forward.

Tom: It is a dawn of a new era, Chuck, where, I sort of imagine that, five or ten years from now when I'm talking to my kids, they will look at me puzzled as to how it was that we only screened for four cancers, commonly. How, how could that be?

Chuck: Today, we’re going to continue our conversation about cancer early detection.

Early detection is a broad term we use to talk about the tests and screenings that can pick up the presence of cancers in the body. That might take the form of a mammogram or a pap smear or a colonoscopy. These are essential tools we've had for a long time to improve outcomes for patients, and many people are alive today because they underwent these tests.

But these approaches are limited, mostly because they test for only one cancer at a time. So if you want to be tested for colon cancer, breast cancer, and cervical cancer, you need to undergo three different tests on three different days. The other problem we have is, to some degree, there's a lack of precision. Not every abnormal mammogram is breast cancer, and not every breast cancer will show up on a mammogram, for example.

But the needle is moving – in our last episode, we talked with Dr. Nick Papadopoulos about research he’s been doing to better understand how cancers can show up in the blood, long before symptoms arise.

1

Today, we’re going to hear about a new blood test that’s available right now, for just about anyone who wants it. It’s called Cancerguard, and it screens for more than 50 cancer types.

One of the people who developed this test is Dr. Tom Beer. He’s the Chief Medical Officer for multi-cancer early detection at Exact Sciences. He is also an adjunct professor of medicine at the Oregon Health and Sciences University Knight Cancer Institute.

Here’s our conversation.

__________

Chuck: Tom Beer, it's great to see you. And thank you so much for joining us. Tom: Chuck, it's great to be with you.

Chuck: Tom, you and I have known each other for a long time, have collaborated on many projects over the years, and I'm really excited about the work that you're doing.

You're confronting a problem that is, I think, long overdue to confront, let's just put it that way. We'll get to the new products and all of the great science, but let's go back to the beginning, and just on basic principles: why is early detection a good thing in cancer?

Tom: You know, for many cancers, outcomes are dramatically different if a diagnosis can be made early. Particularly when we think about solid tumors, the common cancers like colorectal, lung, breast, prostate, and others, we know that a localized tumor can be treated with the intent of cure. That's often surgery or radiation, perhaps some medications along with them. And many, many, people can become cancer-free and stay cancer-free long term if the cancer's diagnosed early. So the real fundamental idea behind early detection is to catch cancers at a point where treatments can be much, much more effective.

Chuck: And we have many successes in the area of early detection and have for, for decades, to some degree. But there are many cancers that just do not have an early detection strategy. Tell us about what the gaps are in early detection.

Tom: Sure. So as you mentioned, we have notable successes, but at the same time, routine guideline recommended screening is only available for four

2

common cancers, and that's cervical, breast, colorectal, and lung cancer in smokers. That leaves the majority of cancer diagnoses and the majority of cancer deaths due to cancers that we don't screen for. About 70% of cancers diagnosed and 70% of cancer deaths occur from cancers that we do not screen for.

Chuck: So your company, Exact Sciences, recently released a test that can detect multiple cancers at once, through a simple blood test.

So, first of all, explain to individuals why a blood test would be superior to doing a CAT scan or a MRI or something like that.

Tom: One of the things that we've learned over the last several decades is what makes cancer tick, what are the alterations in the DNA and the proteins and other components of cancer, and which of those are released in small quantities into the blood.

The second thing that makes it possible for us to pursue this is the technology that's emerged for measurement of these very small quantities of biologic substances in the blood. So that's what's made blood tests possible.

Now you asked, why are blood tests superior to imaging, for example? And I think it's more complicated than that. Blood is not going to supplant mammography, for example. But for all these other cancers that we don't have a screening test for, blood offers an excellent opportunity to expand the reach of screening.

And it's certainly simpler and easier to deliver than imaging everybody in the country. It's less costly, doesn't involve exposure to radiation, which has downsides. So it allows us to focus that more intensive evaluation for the patients that really need it.

Chuck: So this knowledge about the biology of cancer, along with the technological developments around blood testing – in other words, the ability to detect DNA – allowed you to develop this multi-cancer blood test that's called Cancerguard.

I wonder if you could tell us a little more about the process of developing this test. For example, what was the population you tested this in? And what were the sort of statistical methods you used to prove that it actually has a benefit?

3

Tom: So our current test is developed on the basis of a large case control study in a broadly representative population aged 50 to 84. And that's where we're focusing our tests.

There's nothing magic about 50, but we thought for the general population, that is the right place to start. That is the group that has 1-1.5% or higher risk of cancer per year. And so that's what we would expect to make the biggest difference.

The test that we've made available is not restricted to that population. So individuals who are younger but have elevated risk of cancer for some reason can certainly access that test as their physician determines. But the population we've got data on right now are the general population age 50 to 84. And that includes high-risk and low-risk every kind of risk. We didn't exclude anybody from that.

Chuck: Can you walk us through the numbers now for individuals who are hearing this and they're thinking: will a blood test accurately detect a cancer? How likely is it to detect one if it's there? How likely is it to miss one if it's there? And how do you move through that decision making process?

Tom: In the study that underpins the launch of the Cancerguard test, we saw a sensitivity – for all cancers except breast and prostate, which we excluded from our indication – at 64%.

Chuck: So just to clarify, sensitivity is “positive in disease” is how I remember it. So it's the number of people who actually have the disease will have a positive test.

Tom: Exactly, so that 64% sensitivity, meaning two out of three cancers were detected, is not equally distributed along the continuum of cancer types. What we see is that some of the most aggressive cancers tend to secrete more DNA and sometimes protein biomarkers into the bloodstream. And so they're actually somewhat easier to detect. And then some of the slower-growing cancers, breast, prostate, small-volume kidney cancers, the sensitivities tend to be lower.

Chuck: So that's a really important point. It has to do with how rapidly the cancer may be growing. A more rapidly growing cancer is going to have more DNA and protein coming out of the cells, entering in the blood, making the test more sensitive or more likely to pick up those abnormalities.

4

Tom: Absolutely. In general that would be true. And one of the strategies that we've taken to address that variability is to use a multi-biomarker class approach. So our test is looking at DNA as well as protein markers. We believe that gives us, to use a colloquial term, more shots on goal, and we intend to continue to evaluate additional biomarker classes as we move forward with this technology.

Chuck: And how many of the cancers that you're detecting, we talked about them being the rapidly growing ones, perhaps the more aggressive ones, but how many of those cancers that you're detecting with that sensitivity are those that fall into the classification of: We don't have another test for these cancers?

Tom: Yeah, so ones that we're talking about here are cancers like pancreatic cancer, ovarian cancer, lung cancer. And remember, we do have screening for lung cancer, but only in smokers – and frankly, folks are just not taking advantage of lung cancer screening very much in the United States, although there is a screening test, and it's a really important one – gastric esophageal liver, those are the cancers that tend to be higher secreters where the test generally has a higher sensitivity.

Chuck: We're moving towards a situation it sounds like, where a patient – or I shouldn't call them patients –an individual, can just decide they want to get this test done and they can interface directly with the company and get the test done without going through their doctor. Correct?

Tom: Yes, in a manner of speaking. So the test is a clinician prescribed test. It's by prescription, but we now have the ability for folks to go to Cancerguard.com, learn about the test, and request it. On the back end of that request there's a telehealth medical provider who'd be responsible for the test order and the necessary follow-up and would be available to answer medical questions that people may have. So we do have it available for folks directly with medical professionals behind it.

Chuck: So individuals who are interested in this approach would be able to go to your website, have a consultation with a medical professional, decide if they are appropriate for the test, and if the test is appropriate for them. And if so, the test could be done. And then what happens?

Tom: If a test result indicates the presence of a cancer signal, which we expect to happen in 1-2% of people that are tested. So 98 to 99% of folks taking advantage of a test like this should expect a report that says: “Result is negative” or “No cancer signal detected.”

5

In that event, we very strongly and diligently recommend that folks continue their recommended standard of care screening. The last thing we would like is for a negative blood test to have folks skip their PSA testing or colorectal cancer screening. Those are really complementary.

For the positive result, what we want to see is first and foremost an interaction with a healthcare provider where the patient, first of all, will hear: ‘this is not a cancer diagnosis. This is a signal that requires a follow-up, there may be a cancer, but it is not a diagnostic test.’

Chuck: That's a really important point, this is not a test to diagnose cancer.

Tom: Yeah, so when the Cancerguard test returns a positive cancer signal detected result, we would like folks to first and foremost see their healthcare provider to understand what the result means. Get a routine history and clinical examination. That might reveal a clear clinical clue where to look. And then if there are no clear clues from that basic evaluation, we focused on imaging as the strategy for resolution of our tests. So folks get a CT scan from neck to pelvis, and as a backstop, if the CT scan doesn't reveal a cancer, they get a PET scan.

Chuck: Got it. Let me ask an obvious question, Tom. Why is a test like this so important?

Tom: Well, Chuck, let me tell you a story that's personal and it's on my mind every day. And that's a story of one of my wife's dear friends, who, like my wife, was a middle school teacher, and retired about a year ago after more than 30 years of service in our local middle school teaching sixth graders.

We knew him well, my wife was the Girl Scout troop leader, and he was the best helper dad for many years. And, you know, six months after he retired, he received the diagnosis of stage four pancreatic cancer and he's currently undergoing chemotherapy.

And, it's just been a heartbreaking development that serves as a very personal reminder for me that he may have benefited from the sort of test that wasn't available when he needed it a year ago, but is now available and, and is going to become more and more widely available.

So, that that's not a story of someone who derived a benefit from the test, but it's a–

Chuck: Story of why we need the test.

6

Tom: – story that's near and dear to my heart for somebody that really could have used it.

Chuck: That helps me a little bit transition into what I would think of as a vision for the future of early detection, which is: it's one thing to diagnose a cancer early so that maybe we can do surgery or radiation or chemotherapy or whatever the case may call for. But there are potentially opportunities for patients to detect a cancer very early, have a treatment where the treatment is not quite so radical – it's not removal of the organ, it's a vaccine or it's a dose of a hormonal approach or some chemotherapy. So tell us a little bit about how you think the future's going to play out. Are those studies underway, et cetera?

Tom: One of the things that we sought to understand is: what would be the impact of the Cancerguard test if it were widely adopted? And how would the spectrum of cancer change? And we have a wonderful mathematical modeling team that's able to construct computer models of reality, if you will. And our team developed a mathematical model of cancer in the United States that included many cancer types and asked the question: what would happen in the United States to the burden of cancer if we added Cancerguard to the current screening test that people have available?

Over a 10 year period, we saw a 42% reduction in stage four cancer, meaning cancer that is metastatic to distant sites, the most advanced form of cancer, and that is true across a number of cancer types. That reduction in advanced metastatic cancer translates into a predicted 18% reduction in cancer mortality.

Chuck: Let me just pick up on that. About 600,000 Americans die of cancer every year. So if we optimize, based on this, to 18% reduction in mortality. You’re looking at about 110,000 people not dying of cancer every year. That's 18% of roughly 600 and some thousand.

Tom: Yes, that is what the model predicts. It does assume that everyone takes advantage of Cancerguard or a test like it on an annual basis. But yes, it's a really large impact. And not only would we see a reduction in mortality, but we would shift diagnoses to earlier stages where treatments can be more effective, and associated with fewer adverse effects and less expense. And innovation could drive that benefit even further as researchers focus on developing even better treatments for early stage cancers.

Chuck: So I like to focus on the big numbers, right? And, 110,000 lives saved every year in the US, times 10 years: that's over a million people who are alive

7

because of early detection. And I think anybody would agree that that's good news about cancer.

Tom: It is a dawn of a new era, Chuck, where I sort of imagine that five or ten years from now when I'm talking to my kids, they will look at me puzzled as to how it was that we only screened for four cancers, commonly. How, how could that be?

Chuck: You think about it, Tom, you know, you and I have had these conversations. You think about the drugs you and I have helped develop that are being taken around the world by people that we’ll never meet. But there are people out enjoying life today, doing stuff that has nothing to do with doctor visits, nothing to do with cancer, because of advances against cancer.

And the thought of a million Americans who are alive and well and hopefully living productive and happy lives because of these tests is a tremendous step forward. It must be a really good feeling for your company. And I wish you all the success in rolling it out and getting it implemented. And I should also say, I think we also look forward to the iteration, the competition, the further study that make these things even better over time. So 18% might actually be a low estimate when you think about it.

Tom: I hope so, Chuck, and it's so good to be with you and get a chance to talk about my professional passion with you.

________

Chuck: That was Dr. Tom Beer, Chief Medical Officer for multi-cancer early detection at Exact Sciences.

I think this is a big step forward, honestly. We now see commercially available multi-cancer early detection tests that people can get. They can discuss it with their primary care doctor. They can have this test done at any point.

And that is very, very promising. It suggests that we're at a sort of a new era of cancer screening where we're getting beyond this linearity problem of thinking about a cancer we want to test; for breast cancer. Doing a test that's specific only to that cancer: a mammogram. Now we just do the blood test and we have the potential to detect up to 50 different cancers. And if you do the math, you'll realize that many of these cancers just simply do not have any other kind of screening or early detection test. So I think that's a big deal.

8

I think what we don't know is how well this is going to play out in the primary care world. Are we going to see challenges regarding unnecessary procedures done in response to this?

Are we going to see rigorous clinical trials and outcomes analysis to determine are we saving– or how many more lives are we saving with this early detection test? But as far as the technology goes, it's very, very encouraging. And I do think this is a pretty significant leap forward. And we'll all need to continue to follow this story over the many years to come, hopefully many future episodes of the Good News About Cancer.

So thanks for listening to this episode of the Good News About Cancer.
I'm Dr. Chuck Ryan at Memorial Sloan Kettering Cancer Center in New York.

The views we express on this show are our own and do not represent the views or opinions of the institutions where we work.

Our production partner is CitizenRacecar. This episode was produced by Anna Van Dine with post-production by Alex Brouwer. Thanks to Lilly for supporting the show.

There's a whole lot more good news to talk about, so make sure you subscribe to this wherever you listen to your podcasts.

We’ll be back again soon with some more good news about cancer.

9