Teamwork in Oncology Spotlighted at ASCO

Medscape

a day ago

This transcript has been edited for clarity.
Mark A. Lewis, MD: Hello. I'm Dr Mark Lewis, director of Gastrointestinal Oncology at Intermountain Health in Utah. Joining me today is Dr Stephanie Graff, director of the Breast Oncology Program at Brown University Health's Cancer Institute, and co-leader of the Breast Cancer Translational Research Disease Group. Today, we would like to talk to you about the latest updates from the 2025 ASCO Annual Meeting.
Stephanie, it's a true joy to sit down with you. I always look forward to ASCO. I sometimes explain to my patients that it's like the Super Bowl of oncology, and I don't think that's hyperbolic. It's the largest meeting of the year.
One of the true advantages is getting to network with people like you, but also — I don't know about you — I get a real tangible sense of progress, and I often tell my patients, 'Listen, I'm going to go to this meeting. I don't want to over-promise and underdeliver, but I think there's a real chance that I'll bring back something new that might affect your care.'
There are the big four tumor types in oncology, breast, lung, [gastro intestinal (GI), and genitourinary]. You practice above the diaphragm, and I practice below the diaphragm. As we might talk about in the Venn diagram, I think we overlap. I'm just curious what's exciting you at this meeting?
Stephanie L. Graff, MD: In breast oncology, there's been a large amount of really exciting news. One of the ASCO plenary sessions, which we haven't heard yet, is SERENA-6, which will be looking at camizestrant with circulating tumor DNA (ctDNA). That'll be exciting.
We're getting updates on overall survival with the INAVO120 regimen. We saw this morning that it improved survival, which is great. We also are going to be seeing data looking at trastuzumab deruxtecan in HER2-positive breast cancer in the first line and then other data looking at targeted therapies for things like PI3 kinase.
Our first oral [abstract] PROTAC, Dr Hamilton presented today, also showed improvement in progression-free survival. Many things like that are exciting and certainly starting to change practice. Pembrolizumab and sacituzumab [are] changing practice in first-line metastatic triple-negative breast cancer. There's so much and it's a really great breast oncology ASCO.
Lewis: I'm so glad to hear that. There are a couple areas I think that we definitely overlap. I'm curious to get your thoughts on ctDNA. My sense as a GI oncologist is that it is a very prognostic biomarker, but it is not always demonstrably predictive.
My real reservation in using it, to be honest with you, is: Number one, I don't think it entirely supplants our traditional clinical pathologic understanding. For instance, as a GI oncologist, if I think someone has high-risk stage III colon cancer and their initial postoperative ctDNA is negative, I'm not entirely going to abandon my approach to their adjuvant therapy.
Also thinking about it as a patient, we're sometimes telling these people that they have literal subclinical disease. You can make the argument, 'Well, why wait until cells aggregate to the point that you can see them as an actual tumor on a scan?'
On the other hand, I worry sometimes about the psychological impact of ctDNA. As you said, we'll hear about SERENA-6 tomorrow. I think that's a really interesting study in the sense of letting patients be aware of emerging ESR1 mutations that are conferring resistance to aromatase inhibition. I'll be really curious to see the outcome of that study and whether that's a meaningful change for the patient, because I think we sometimes actually underestimate the psychological weight.
Graff: It's interesting. In breast oncology, we've benefited from a wealth of patient advocacy, driving a wealth of progress, funding, and advancing science, which has been really beneficial in our field. We actually have done research looking at how the psychological impact affects how patients handle disease. I think that, historically, you can imagine a time in medicine when people thought, 'Oh, those sweet little girls, we shouldn't weigh them down with the worry about cancer.' That has borne out to not be true.
When we think about telling people the results of a mammogram that needs additional imaging or biopsy, or that they have dense breast tissue or that their mammogram needs additional follow-up in 6 months, none of those things actually increase or decrease a patient's worry.
Lewis: Interesting.
Graff: What helps is just open and honest communication. I think what's more important is that we empower physicians and oncologists with the tools to actually understand what these tests mean and how to communicate effectively with patients about them. I think patients are going to be worrying about the fact that they have cancer.
Good test or bad test, that patient knows the next test might not be the same. Good test or bad test, their cancer could have a different outcome down the roadway. They're going to worry. I don't have cancer and I worry. I worry about my kids. I worry about my house. I worry about the weather. We all worry. I think that just having the tools to explain what's going on is probably the most powerful thing that we can do.
Lewis: That is such a wonderful anecdote to literal and figurative paternalism, and you're absolutely right. We already have these points of apprehension in patient care and diagnostics, and I think ctDNA potentially adds to that, but we can use the same methods of counseling that we've used for all these other tools. That's so well said.
I also wanted to tell you — and I really, really mean this — that I view breast medical oncology as aspirational for the rest of solid tumor oncology. When you were mentioning trastuzumab deruxtecan earlier, one of my most vivid memories from ASCO meetings of any year was the plenary session where DESTINY-Breast04 was presented.
I remember being part of the standing ovation for that trial, even though I don't treat breast cancer anymore, because I thought, 'Wow, we are really making progress in biomarker-driven care.' The other reason I view you as aspirational is we are not yet at that standard in GI oncology, at least, where it's a foregone conclusion that we would know all the biomarkers that we need to know.
One of the interesting conversations I have with patients now is on pathologists as our silent, or at least unseen, partners. I think you would agree that you would almost never treat a patient with metastatic disease without knowing ER, PR, and HER2 status.
Meanwhile, over in GI oncology, I'm sometimes having to ask for these things to be done that would be relevant to my patients, say KRAS mutations or BRAF mutations. To me, it seems like it should be as reflexive for me as it is for you as a breast cancer oncologist.
What I'm getting at here, too, is this is back to how we have conversations with patients. I think patients need to understand, again, that biomarkers are a huge part of how we personalize their care, even though they might never actually meet their pathologists.
Again, I just wanted to tell you, because I don't often get to sit with you, that the way that breast cancer oncologists — and to your own point, patient advocates — have kind of pushed things forward, it's a rising tide that lifts all boats. I often use your field as an example of where we should be.
Graff: It's ironic because I have maybe the opposite perspective. As a breast oncologist, I feel like, here we are in 2025 with all these amazing genomic ctDNA and RNA assays, and we're still using ER, PR, and HER2, which is — spoiler alert — literally dumping ink on slides, right? It's immunohistochemistry.
Our thoracic oncology colleagues are using true genomic-driven care to look at ROS1 , EGFR , and all these different things to say, based on this profile, this is what you're going to get. We're like, well, we have to wait for that ER to come back. I'm a little bit jealous that some fields have more genomic-driven care than breast does, but you're right. Breast was definitely a pioneer in biomarkers.
DESTINY-Breast04 is an interesting example because, if anything, it shows that the biomarker doesn't matter, right? Trastuzumab deruxtecan is a HER2 antibody, and as it turns out, it works great for HER2-positive disease, but it also works great for HER2 not-so-positive disease.
DESTINY-Breast06 now includes ultra-low, which is zero with just a little bit of fuzzy in the background. We're seeing that maybe we're not getting our biomarkers right after all.
Lewis: So well said. I remember thinking about the effect in ultra-low and thinking, man, how strong is this bystander effect? If the chemo payload is being delivered to barely present HER2 receptors, it must be really potent indeed.
I often think that we're actually putting a large amount of credence in what our pathologists tell us. For instance, like you said, immunohistochemistry is very qualitative, sort of semi-quantitative. Again, with things like PD-L1, it's funny how we all have sour grapes to other tumor types.
Thinking about continuous variables, we can always debate the appropriate cutoff. Pathologists have actually warned us at this very meeting. I remember Anirban Maitra standing up and saying, 'Listen, you guys need to realize, as pathologists, the number that we give you for PD-L1 expression, for instance, that's our impression on that day, on that slide. You really shouldn't take it to be gospel truth.' Again, I think we're still finding our way with that.
Graff: We've seen, in breast oncology, a presentation at this meeting looking at if that's the forefront for AI, right? Is that where artificial intelligence is going to be able to augment our ability, because again, we heard in the opening session that AI should be a tool that is an agent to advance human skills.
If AI can help augment the eye of the pathologist, enhance the skills of the microscope, and move HER2 zero to HER2 ultra-low with more accuracy than the naked eye or more robustly in global centers where access to those stains aren't as readily available, then AI is advancing care for everyone equitably around the globe: the same global population that's participating in these trials and bringing them to our patient population.
Back to biomarker-driven care, I think it just comes back down to patient communication. All of these tests take time. Even in breast oncology, sometimes my patients have to wait. They have to wait for ESR1 . It's a mechanism of resistance. I don't have it until their disease progresses and I can send that test out.
That means that sometimes they have to have some patience while we wait and make sure that they're a candidate for the right therapy at the right time. That requires partnership with a bunch of people on my team. The staff that draw the blood and the mail room staff that ship it out to the right team. I'm so thankful that I have a huge wealth of people that make the cancer center work.
Lewis: So well said. I often tell my patients that oncology is a team sport.
Graff: Yes.
Lewis: I think the last thing I wanted to say is that you and I have talked a little bit about the pace of progress as a wonderful problem to have. I'm curious, [going] off your comment about sort of global equity, how do you feel like that plays out in sort of clinical trial design?
Graff: The breast oncology community discussed this today as some data were revealed. An interesting problem that we're starting to have in breast cancer is the rapidity of new agents relative to the rapidity of trial accrual. This means that, if it takes a year to design a trial and get regulatory approval, and then another year to accrue and then another year to read out results, by then there have been 27 new drugs added, right? I think we had 25 regulatory approvals last year in the US, or something like that, in oncology.
Whatever the standard-of-care control arm was in the study 3 years ago when that trial was designed is laughable. I'm going to use the example of second-line HR-positive breast cancer. We have two problems. Problem number one is that the standard control arm is fulvestrant. When many of these trials were accruing in 2020 and 2021, that was the standard of care.
Now, we have ESR1-targeting agents. We have PI3 kinase-targeting agents. We have data that extending a CDK4/6 inhibitor is efficacious. We have evidence for earlier trastuzumab deruxtecan for patients that maybe aren't so endocrine sensitive. We can always extend everolimus into that space. There's all this other stuff, including oral SERDs. There are so many different directions we can go. I don't even remember what all I've listed [to] at this point.
We're getting the next generation of medicine, but they're still being compared to fulvestrant.
Lewis: Right.
Graff: We're looking at these results, saying, 'Well, great, you beat that drug we used back in the late 1900s.'
Lewis: Right. Yes.
Graff: Now, I think that another problem is that global angle, which is that not all of those new drugs, although almost all of these trials are global trials, they're accruing these from international countries. Not all of the regulatory agencies have approved them internationally. Not all of the payers have approved them internationally because they meet different benchmarks around the globe.
Lewis: Yes.
Graff: That standard-of-care arm isn't available as we advance. Again, trial design gets complicated because if we want the control arm to be the US standard of care, and that's different than the German standard of care, the Indian standard of care, the Kenyan standard of care, or the Argentinian standard of care; then we have to make sure that they're connected with that standard of care. We have to make sure that they're comfortable delivering that standard of care and figure out what that really looks like.
Lewis: I think where I completely agree with you is you have to walk before you can run. It's really exciting to see the sophisticated assays like ctDNA, but I'm sitting here thinking, based on your comments, I can't even guarantee that I'll have mismatch repair protein status in my patients with colon cancer.
Again, we have to take this in a stepwise fashion. You're right that, for all the excitement that we understandably and should feel at meetings like this, we do have to temper our enthusiasm a little bit and be practical in the real world.
I have to say, Stephanie, it's just a delight to sit with you. I think you really are a true exemplar of shared decision making. Again, it really, at the end of the day, doesn't come down to the primary site. Yes, you're a breast oncologist. Yes, I'm a GI oncologist. A rising tide lifts all boats, and I think, as we also heard this morning, there's a difference between irrational exuberance and unjustified optimism, and then there's legitimate hope. At least what I feel at these meetings, and I strongly suspect you do too, is legitimate hope for our patients.
Graff: I agree.
Lewis: With that, we'll close. Again, thank you for joining us. We hope this was a helpful summary of what we've been hearing today at the ASCO 2025 Annual Meeting. Thank you.