DETECT-A Study: Advancements in Early Cancer Detection

Transcript:
Elizabeth O’Donnell, MD: All right, Dr Buchanan, I’m going to draw you into the conversation now. Could you discuss the DETECT-A study with us, please?

Adam H. Buchanan, MS, MPH, CGC: Sure. So this is one of the early trials…. This is a prospective interventional trial. It was done in a single center with a single-group design. And because it was early, it was really focused on feasibility and safety. So feasibility: How well is it fit with the flow of care? What is the process and the rate of return and diagnostic resolution and safety questions along the lines of whether the unsupportable rate of field diagnostic investigation occurred or whether individuals who had a negative test result were discouraged from doing the standard-of-care screening or a negative outcome. That certainly raises concern in the field. And then, of course, there was a focus on test performance, all the normal performance characteristics that we think of with cancer screening tests along the lines of specificity, sensitivity, positive predictive….

And this was an evaluation by a multibiomarker InCyte test [using] both DNA and different amplicons as well as protein biomarkers that are often known to be associated with the presence of cancer. And we enrolled about 10,000 women, ages 65 to 75, in a single site, Geisinger, and administered the test, along with some baseline data collection on health behaviors, cancer screening, family history and so forth, and then followed both negative and positive participants over time. Initially, we followed them for a year, and we wanted to determine of those who were positive for developed cancer and those who were negative who developed cancer.

And I think we learned a few things along the way. Of those roughly 10,000 participants, about 1% had a positive test result. The design of the testing protocol itself was intended to maximize specificity. So there were a couple of rounds of testing to try to reduce artifacts of testing and to increase the rate of positive predictive value there. We disclosed results after we had reviewed them with essentially a tumor board or multicancer early detection board to try to read out those elevated protein biomarkers that might have been noncancer ideology. And so with those 1% testing positive, we found that the InCyte test added to what we found through standard-of-care screening. So 26 participants were found to have cancer diagnosed through a positive test, 24 were found because of standard cancers, standard-of-care screening. So essentially double the rate of pickup from what we typically see for standard-of-care screening.

In terms of outcomes like safety and visibility, we found that the rate of diagnostic investigation is low, under a quarter of a percent. So that means fewer individuals going on to potentially risky activities like biopsies or invasive procedures. And I also found that from the perspective of performance of recommended management, we took a look at mammogram adherence before and after testing and found that there wasn’t any difference before and after. So some amount of encouragement there for the concern about not discouraging the recommended care. I think a few other notes here about findings of a particular trial in terms of performance. The specificity was acceptably high, about 99.5%. That’s what you want to see in a test like this. And the positive predictive value, when you combine both the test itself, the blood test, as well as the imaging that was used for follow-up, it was in the 40% range. So compared with some existing standard-of-care screening, that’s an improvement. And positive predictor varied from what we often see here. We also found that sensitivity across its stages of diagnosis was about 25%. And again, that’s combining both from 1 test and imaging. And so I think that highlights that there is absolutely room for improvement there and sensitivity and highlights a key difference between MCED [multicancer early-detection] testing and single-tumor screening in terms of what’s considered acceptable for sensitivity. I would also highlight the performance by tumor type varied quite a bit and emphasizes the importance of a complementary approach. So for example, the MCED tests that were evaluated with the PROTECT-A trial did not detect many breast cancers, but there were several participants found in breast cancer through standard-of-care screening. So definitely highlights it was complementary and in particular the ones that were diagnosed through standard-of-care screening tended to be early stage as well. So again, as Dr Ebbert pointed out, this complementary approach to using the tools we already have and having a new tool seems like it bears promise. So I think those are some of the key take-homes that will inform both our future trials and how we might implement those trials.

Elizabeth O’Donnell, MD: Maybe you comment on the feasibility of this. You said this was all done within your health care system. What did you learn about the feasibility of doing MCED testing?

Adam H. Buchanan, MS, MPH, CGC: The diagnostic resolution typically proceeded along a typical path. So once we moved on from the blood test itself to the PET-CT that was used as a follow-up to localize the source of the tumor, then the rest of the process was more of a standard of care with the way to work up a tumor in a particular location. So that seemed to fit well with the clinicians who typically are involved in that process. We, because of the study design and the extra caution to increase specificity, learned that you need to get to a shorter turnaround than the total process, so Dr Beer mentioned that 2-week turnaround that the various players in the space are shooting for. We didn’t have that in this trial. It’s clear that that needs to be the case to be consistent with other cancer screening in this space.

Jon O. Ebbert, MD: Certainly, lots of foundational knowledge laid down by…DETECT-A.

Transcript is AI generated and edited for readability.