Expert: Increasing Use of Circulating Tumor DNA in Oncology Will Take Time

In an interview at the American Society of Clinical Oncology (ASCO) 2022 Annual Meeting, Bruce Feinberg, DO, vice president and chief medical officer at Cardinal Health Specialty Solutions, discussed the use of circulating tumor DNA (ctDNA) and how it can be used in colorectal cancer. Although it has clear benefits when monitoring and managing cancer, Feinberg said more widespread use of this testing method will take time.

Your research found that nearly half of respondents did not use ctDNA to make treatment decisions in colorectal cancer. Why is this?

Bruce Feinberg, DO: So, this is going to be something that would likely be trending over time. And this is not unusual for our research. There's just a certain learning curve, and a certain amount of time that it takes for new science to get fully adopted, and often in that first wave of data there's a little bit of hesitancy. Is there enough data? Do I need to see a confirmatory study? Was the study performed large enough? Do I want to see it in a different tumor type? And so, there will be physicians who will be early adopters and understand the science and want to start using it. And there will be physicians who will be a little bit on the fence, and also physicians who will say, “This is not ready for primetime. It's fascinating, you know, but come back to me in 10 years, and we'll see.” And we saw some of that.

I would say that we saw the 50% maybe in a more favorable light. So, we saw the glass half full, not half empty, given the fact it really is a single tumor type. That's one, although the research is much broader, but one that's come into the mainstream with a large well-defined trial, in which multiple experts in the field have weighed in. We thought that that speaks favorably to the recognition that this is something which could move forward and move forward quickly. I still think it could be 5 to 10 years for it really to replace more traditional ways of assessing treatment response. I think we're going to see it sooner in blood malignancies, multiple myeloma in particular. But even now that we're using it, in areas like blood-based cancers, like multiple myeloma, there still is hesitancy to base the full decision making on the result and we're still doing the traditional processes in addition to that test, but they're always at a point of transition. And I think we're well on our way now. Because the science is there, the science has been validated, it's just going to take a little bit of time to kind of move that needle, where we'll have the full adoption.

Is ctDNA used in other diseases, and how widespread is this use?

Bruce Feinberg, DO: So, in the hematologic malignancies I would say it is already primetime. It's used, but we haven't gotten to the next step, which is at what point is its effectiveness in being able to measure the amount of cancer? So let's just say that we determined that we had 2 consecutive readings, in which there is no measurable cancer and, again, at this level, you know, we're down to far below anything that could be seen on an X-ray. At what point do we say, okay, based on that we're no longer going to treat, as opposed to, “Oh, that's great. And we're going to continue treatment anyway.” So, we're not quite there, where we're basing our full decisions on that and that's going to take more time.

So, you'll see a study will be done in which patients who had, let's say, 2 consecutive levels which were unmeasurable on minimal residual disease down to multiple logs down of a tumor regression, and we’ll actually discontinue half of those patients on further therapy, the other half will continue. And then we'll see over 2 years what the outcomes are. That's what's going to start to happen. Now, how do we now take this tool which has been validated, which is being used, and then start to apply it where it really will influence the way in which we treat the patient going forward?

What steps could be taken to improve utilization of ctDNA in colorectal cancer?

Bruce Feinberg, DO: What made medicine modern is the concept of the randomized controlled clinical trial, the idea that we weren't going to make decisions based on anecdote. I observe this, so I'm going to try this again on this patient, I thought it seemed to work in that patient, I'm going to tell my colleague, and there's this groundswell. I write a letter to the editor, a case study of 3 patients, and suddenly it starts to be adopted. That was the world of medicine up until the mid-1980s, to some degree. The introduction of randomized controlled clinical trials really elevated it. We're going to remove all biases of the observer, you're not going to know if the patient got the treatment or they got the sham, if they got the experimental drug or they got the standard of care. And patients won't know and doctors won't know—double blinded. And we're going to have independent assessments done, what's called blinded independent review of the X-rays of the pathology. So, again, we're going to have a central source looking at everything and looking with the same eyes. So, we don't have all these different investigators with their own little ways of doing things. And we introduced a rigor to the process. Now, there were problems with that, and the problems were that it took time and it took money. Now we're finding ways to expedite and accelerate those processes, but they still represent a scientific rigor which we need to continue. And that's what's going to be done with ctDNA. It's going to be applying, now that we know that the science is sound, doing those kinds of studies as accelerated as we can do them, in order to prove the effectiveness of it as a tool that's going to directly impact the care of the patient, as opposed to information for information’s sake.

What does implementation of ctDNA look like in the community setting versus the hospital setting? What are the benefits or obstacles of this environment for ctDNA testing?

Bruce Feinberg, DO: So, fortunately, the ctDNA technology is readily available now. And there are multiple commercial labs that do it. And so, it's no longer something which can only be done in an academic institution, by that hospital or a sophisticated laboratory. So, it's readily available to all providers in whatever sphere they're working in. And therefore, it's a readily available tool for the management of all patients. So, I don't think we have any barriers to access of the technology. I think the barrier will be really overcoming what are reasonable health care provider reservations with a new technology.