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ESMO, Efficiency, and Evidence: A Look Ahead at New Data and Important Updates
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Released: October 15, 2025

John Marshall
John Marshall, MD
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ESMO, Efficiency, and Evidence: New Data, China’s Science Leap, and Leucovorin and Autism

 

John Marshall, MD: Hey everybody, John Marshall from Oncology Unscripted. There is so much going on right now that we're gonna need a full hour-long show, but we're not gonna do that to you. We still promise short bites here and there of the stuff that's going on, just to make sure you're in the loop. I'm sure you are.

 

But let's start with a little science. And the science we wanna focus on is the upcoming ESMO meeting. We've looked at the leading abstracts that are gonna be presented there, and there's not gonna be a lot of surprises about the content. There's a lot of innovation in precision medicine and immunotherapy and different diseases, and positive randomized trials, and some exciting early-phase clinical trials.

 

But what I think is worth noting is that a pretty high percentage of the science that's being presented at ESMO actually comes from China—Chinese pharmaceutical companies sponsoring it, China's institutions running the clinical trials. And there's been a lot of discussion about the quality of Chinese data.

 

Just recently, on September 23rd, Scott Gottlieb—who used to be, of course, the head of the FDA—did a very nice opinion piece in The Washington Post about the impact of Chinese drug development. The quality wasn't actually that bad—it was just less expensive. They were able to do clinical research much less expensively than we can here in Western society, if you will.

 

So, it's not so much intellectual innovation—it's efficiency in getting answers out. His whole editorial is about: how do we reshape and reprioritize our own clinical research infrastructure? How does the opportunity of a, I don't know, a world turned upside down in terms of regulatory oversight, et cetera, give us a chance to maybe improve the process, to lower the cost of drug development, so that our innovation—which we really still remain the hub for—can actually be brought forward and not create some sort of global intellectual property war, which he refers to, but more: how do we keep up with the pricing structure and the innovations that are out there?

 

So, I encourage you to not only look through the abstracts from ESMO—because there are some very important positive results from that—but also think a little bit about how we, in different parts of the world, even the playing field around the cost of new drug development. I encourage you to read that Scott Gottlieb Washington Post editorial.

 

One of the big abstracts that will be presented is around MRD ctDNA testing and using that technology as a way to define who should receive adjuvant therapy and who should not. Of course, we are interviewing the lead author on that paper, so stick around for that interview. But we clearly can see that genetic testing may, in fact, have a major impact on making us more efficient on who should get adjuvant therapy and who should not.

 

So, I do clearly think that's the evolution that's going forward. You wanna make sure to keep your finger on the pulse of MRD ctDNA testing in the decision-making process for adjuvant therapy and subsequent treatment.

 

I'm lucky enough to be running a protocol here in the United States looking at MRD positivity in patients with colorectal cancer, and others are doing it in other diseases.

 

One of the ways that could, in fact, make that much less expensive is digital pathology. Because it turns out that a digital image of an H&E slide—and there's some fascinating data around this—can actually predict risk almost as well as genetic testing. So, that's very inexpensive. It takes 20 minutes to scan it in, send it off to the computer, AI reads it back, and gives you a risk factor.

 

So, I do want you to also keep a nose out for digital pathology as an impact.

 

But maybe the most unsettled science that I saw in the last week actually was also in The Washington Post. Now, The Washington Post, in one issue, reported on vaccines killing children, our administration down the street is going to be talking about how evil vaccines are—continuing that discussion that their rising costs are gonna break us in the U.S. Our economy is so built around healthcare that the rising costs are eventually gonna break it. And the risk is that what I'm saying right now might land me in the same boat as Jimmy Kimmel—of getting fired. But you know, last night he was back on again. So maybe that will only be temporary. But the science I wanna talk about is this whole connection between, say, Tylenol—acetaminophen—and autism. And the only reason it says “Tylenol” is that Donald Trump can't say the word “acetaminophen.” And so many people out there are affected with autism over many, many decades—even well before Tylenol/acetaminophen was invented. But what really caught my eye is these smaller studies that have suggested that leucovorin—which is folinic acid, okay? It’s reduced folic acid—was helping in some clinical trials.

 

Now, I wanna remind us all that in the United States, in 1998, our diets began to be enriched with folic acid. They did that because there was very good evidence that if you had enough folic acid in your diet and you were pregnant, that you reduced the risk that the baby would have any neural tube defects.

 

So, our entire country is on folic acid supplementation so that we would have a reduced rate of neural tube defects. And for us—or the administration—to now be saying that we should be giving people leucovorin, which is simply a reduced form of folic acid, to try and treat autism is really wild. To the point where the recommendation came out—even this morning—pushing from the White House up to the FDA to relabel leucovorin.

 

Now, I give a lot of leucovorin. I'm a GI oncologist. So, let me just remind you that when we don’t have leucovorin—remember the plant broke, and so we, for a while, didn’t have leucovorin—if you just took folic acid, if you went down to Costco and bought yourself some folic acid and you took it, your body converts it to folinic acid using dihydrofolate reductase—an enzyme we all know and love, 'cause that’s where methotrexate works.

 

So, we’re on it anyway, right? We’re all supplemented through our diet, but also many people take multivitamins and others. But we’re all on folic acid—so much so to the point that side effects from 5-FU in the United States are different than 5-FU side effects in other parts of the world because we're all on low-dose leucovorin, if you will.

 

And so, before we all go crazy—and I know, if you are the parent of somebody with autism or you know somebody, you're tempted to say, “Well, let’s go out. Let’s take some folic acid”—I don't think there's any harm in that. But I think for our administration to change a label based on this amount of data is unprecedented. And I'm anxious about that because it meets a cause that they care about, but you know, it may be influencing how we develop drugs in the future.

 

So, it's science. Yes. Is it early? Yes. Would I like it to be true? Yes. I think we ought to study it further. Should we change a label? I think that’s taking the step too far.

 

So, a lot of science—whether it’s ESMO or in The Washington Post—a lot to learn as we go forward. Pay attention. Value the data that you see in front of you. Qualify it in a way that makes sense to you. And then make your recommendations to your patients and your friends based on that. I think we’ll be better off if we stick to traditional scientific method. Yes, accelerate it. Yes, make it more efficient. But we need traditional scientific method in order to improve outcomes for our patients around the world.

 

John Marshall, Oncology Unscripted.