GU Cancers 2026 | IMvigor011: ctDNA dynamics in MIBC treated with adjuvant atezolizumab

In fact, what I did present is an exploratory analysis of this trial. It was exploring the ctDNA dynamics. To remind the InVigorO11, it was a prospective randomized trial that provides a survival signal testing if ctDNA positivity is a signal that can make the patient benefit from receiving adjuvant atezolizumab. So the trial was positive in patients that have ctDNA positivity when they were randomized to placebo. So InVigorO11 is a trial that after surgery patients having cystectomy if there were like signs of a still active pathology they were monitored with the ctDNA and patients that at the beginning became positive or later on in the follow-up became positive those were randomized and then patients that were negative they consistently followed and these patients are the ones that have not recurred and have not been included in clinical trial. So what we did is try in these two populations, patients that were included in the trial that became positive in the beginning or became positive later on, we have been exploring the differences between this timing related to the outcome. And also one thing that is new that we have been exploring is the concentration of the ctDNA in different settings. What we did in this trial, the first things that were presented is a correlation between the concentration and the timing of the ctDNA positivity. What we see is that the majority of patients are having positivity of ctDNA in the first six months, and the concentration of ctDNA is high. Patients that ctDNA shows up later, those patients have very low concentration of ctDNA. Then we did an analysis trying to correlate the ctDNA concentration and timing with pathology. And in fact, we saw that higher pathological stages at surgery correlates with higher concentration and early positivity of ctDNA. But we saw interesting things like patients with T2. We see T2 usually is sometimes people are questioning if you need to give adjuvant therapy or not. But some patients with T2 disease, they have a higher concentration of ctDNA, meaning that these patients need to be checked and monitored. And then what we did is also correlate the timing of ctDNA being positive with the outcome, this is survival and overall survival. And also the concentration was correlated with the outcome. We saw that the patients that the ctDNA becomes positive sooner in the very beginning, those have poor DFS. So these patients have higher concentration, they recur sooner, and they have poor outcome compared to the patients that the ctDNA becomes positive in the follow-up. The second thing is the concentration. We saw that the concentration impacts on the outcome. We set up like three different levels, patients that were negative, and those were doing pretty well, not recurring, but if you have a ctDNA positivity of less than 0.1 or in between 0.1 and three or more than three, you see that the curves are completely different. Obviously, all these patients that have some level of ctDNA, they recur and then might need systemic therapy. And then, obviously, we analyze the impact of atezolizumab in these different subgroups. We analyze the overall survival, disease-free survival, depending on early versus late ctDNA or depending on the different levels of concentration. We saw that atezolizumab was benefiting all the populations. Patients with low intermediate high concentration, patients having ctDNA early show up versus late. And this has been telling us a bit of the natural history of ctDNA because some of these analyses were done in patients that never received treatment, meaning it’s a way to tell what this ctDNA is telling us. And then what we did is we moved the real kinetics of ctDNA to see what’s the impact of atezolizumab on the kinetics. What we saw that, in fact, depending on the baseline values of the ctDNA, there is a benefit on outcome and on disease-free survival when you give atezolizumab. Meaning patients that are receiving atezolizumab with a high ctDNA concentration, they do much better. And this is translating on overall survival and disease-free survival. In fact, the INVIGOR-O11 is the only trial showing survival benefit when giving atezolizumab in patients post-surgery if they are ctDNA positive.

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