This transcript has been edited for clarity.
Hello, everyone. I’m Dr Bishal Gyawali, associate professor of oncology at Queens University, Kingston, Canada. I’m very happy to share with you some of the most exciting data that I just saw at the plenary session at ASCO 2025.
Before that, I’m going to talk to you about a fantastic new drug called exercisumab. I’m joking, of course. Exercise has been shown to improve the lives of patients with colon cancer. I’m joking that if there were a drug called exercisumab, the data would be so compelling that we’d all want to use it and fund it today.
Because this is not a drug and it’s about exercise, I see some challenges in implementation. I hope that I’m able to convince you that the data are really compelling and we should make an effort so that our health systems will integrate this as a part of cancer care for patients with high-risk stage II and stage III colon cancer who receive adjuvant chemotherapy.
The trial I’m talking about is called the CHALLENGE trial, which was not presented at the plenary but should have been. In this trial, patients who had high-risk stage II and stage III colon cancer, after they completed their adjuvant chemotherapy, were randomized to receive a structured exercise program vs the standard-of-care arm.
The standard-of-care arm patients received health education but did not receive a structured exercise program. The goal of the structured exercise program was to improve physical activity by at least 10 MET-hours compared to the baseline of these patients.
The primary endpoint was disease-free survival. Disease-free survival was significantly improved, and overall survival was also significantly improved. The 5-year disease-free survival rates improved by almost 7%, and the 8-year overall survival rates also improved by a similar amount. The hazard ratio for disease-free survival was 0.72, and the hazard ratio for overall survival was 0.63.
These are very compelling results. If you compare these results with results from other trials, you’ll see that this is a no-brainer. If this were a drug, you would want to use it today.
There are some nuances about this trial that I want to highlight. When we talk about the results, some of the comments were, “Oh yes, I have been asking my patients to exercise anyway.” Exercise improves quality of life, it’ll reduce weight, and these are all known to benefit patients.
I have been telling my patients to exercise, but this trial is not about telling patients to exercise. This trial is about having a formal, structured exercise program. There are particular details.
Patients need to have an in-person visit with a therapist every 2 weeks for the first year and then every month for the next 2 years, so it’s a 3-year therapy program. It’s a scientifically designed and tailored program. It’s not just saying, oh, you should exercise. In fact, saying you should exercise and giving some health education was the control arm of this treatment, not the interventional arm.
The control arm patients were told about this trial, the potential benefits of the exercise, why they should enroll in this trial, and they were given health education materials. An interesting observation is that even the control arm patients had improvements in their physical functioning, VO2, and all those parameters from baseline to subsequent visits.
One limitation is the adherence rate to exercise. We see that the adherence rate kept falling with time. I think that by the end of 3 years, the adherence rate to the exercise program was around 60%-65% in that ballpark, which is a limitation. Having said that, the analysis accounts for all of that.
Despite that limitation, we are seeing this substantial benefit. If you want to compare that with the ATOMIC trial, which was a plenary presentation of immunotherapy plus FOLFOX for patients who needed adjuvant FOLFOX in stage III colon cancer patients, of course, the addition of atezolizumab to FOLFOX improved disease-free survival rates. The primary endpoint here was 3-year disease-free survival, and it improved significantly. It was a plenary, and people were making the argument that this should immediately change practice.
If you compare that with this exercise trial that I just discussed: A, think about the added toxicities; B, think about the added cost; and C, think about how feasible it is to implement. I think it’s a no-brainer that we need to start having health systems funds for a structured exercise program for our patients with colon cancer.
Yes, the atezolizumab data and the ATOMIC trial data look very interesting and this is one of the first advances in treatment of adjuvant colon cancer in a long time. This is for patients with microsatellite instability-high status. We don’t have overall survival results yet. Disease-free survival is a much more reliable predictor of overall survival in this particular setting. I believe that overall survival might be positive, but we also need to know what percentage of these patients got immunotherapy when they relapsed, because immunotherapy is already standard of care for these patients when they relapse.
The other point about this trial is, do they all actually need 1 year of atezolizumab? Probably not. As the discussant highlighted in her talk, in many settings, we are now using neoadjuvant strategies. Using two or three cycles might be enough.
The broader point that I’m trying to make is contrasting these two studies and inviting you to think about how different these are, even in terms of magnitude of benefit. The exercise trial has overall survival, not just disease-free survival, at an 8-year time point.
When I asked Dr Booth about the cost of this intervention, he said for the whole 3-year time point, it might be around $3000 Canadian dollars. This trial was conducted mostly in Canada and in Australia. As opposed to atezolizumab, where a month of atezolizumab alone is going to cost $15,000, so that’s just a perspective I wanted to put forward.
One more thing I wanted to talk about today is the SERENA-6 trial, which was discussed at the plenary session. This is a trial for patients with estrogen receptor-positive, HER2-negative metastatic breast cancer who have been on a CDK4/6 inhibitor plus aromatase inhibitor for 6 months. They were then tested with ctDNA to detect ESR1 mutations early, and if this was detected, then they were randomized to either follow the same treatment, which is the control arm, or get the new drug.
The primary endpoint here was progression-free survival. This was debated often during the season. We have so many debates about progression-free and overall survival, but for this particular trial, progression-free survival makes no sense because this is just detecting relapse early. Detecting relapse early does not always mean that you need to intervene early.
Of course, if you are intervening early, then you are going to prolong time to tumor progression. The progression-free survival in this sense is more like time on treatment with this drug rather than true progression-free survival. You’re just changing treatment early, and the control arm patients are not getting that treatment when they progress.
Measuring progression-free survival alone here felt similar to measuring CA-125, or whatever tumor markers we measure, then instituting treatment early and claiming that patients have a longer time on treatment, when in fact, it’s just lead time bias or intervening early without knowing that it’s going to improve outcomes.
A final trial from the plenary session was the MATTERHORN trial. I want to bring that up as well because this trial was investigating durvalumab plus perioperative FLOT in patients with esophageal cancers. This trial had a significant improvement in event-free survival, but has not improved overall survival yet. It may or may not translate into an overall survival improvement.
The discussant did not cover the limitations of this trial well, and that’s why I wanted to bring it up. There are several factors to consider here. There are other trials in similar settings, where event-free or disease-free survival have improved, but overall survival has not. There is no point in getting super excited about this because it may not translate to overall survival, just like other immunotherapy trials in this space.
The other thing is, we need to make sure what treatments patients are getting at the time of progression or at the time of relapse. Are they getting the right treatment?If they’re not getting the right treatment, then any survival difference can be simply a function of the control arm patients not getting the right treatment at the time of relapse.
If we compare these results with results of other immunotherapy trials, I don’t think the results are substantially different. Yes, an event-free survival improvement is important, but especially in this setting, in this disease, we have seen other trials where disease-free or event-free survival have not necessarily led to an overall survival improvement. We need to be asking ourselves, can we claim that it is already practice changing without having those results? I don’t think that’s the case.
Those are some of my thoughts from this year’s plenary session at ASCO 2025. Thank you.
