ESMO 2025 ctDNA-guided adjuvant atezolizumab improves MIBC survival

medwireNews: Adjuvant treatment with atezolizumab significantly improved the survival of people with muscle-invasive bladder cancer (MIBC) who tested positive for circulating tumor (ct)DNA by serial testing in the IMvigor011 trial.

Presenting the findings at the ESMO Congress 2025, Thomas Powles, from Barts Cancer Institute in London, UK, said that both disease-free survival (DFS) and overall survival (OS) were prolonged with the use of atezolizumab in these ctDNA-positive patients.

Moreover, he pointed out to the audience in Berlin, Germany, that “patients who were persistently negative” for ctDNA had a low risk for recurrence and death.

“These findings indicate that serial ctDNA monitoring can identify patients with [MIBC] who benefit from adjuvant atezolizumab while sparing patients who are persistently negative from unnecessary treatment,” Powles added.

Explaining the rationale for the trial, he said that in the previously reported IMvigor010 study, there was no survival gain with adjuvant atezolizumab in unselected patients with MIBC but exploratory analysis suggested a benefit for those who tested positive for ctDNA after cystectomy.

The researchers therefore investigated ctDNA-guided therapy in the phase 3 IMvigor011, in which 761 patients with (y)pT2–T4aN0M0 or (y)pT0–T4aN+M0 histology and no radiographic evidence of disease after cystectomy underwent serial ctDNA testing every 6 weeks for up to a year. Participants who tested positive for ctDNA at any time were randomly assigned to receive atezolizumab 1680 mg every 4 weeks or placebo for a year, while those who tested negative did not receive any treatment and underwent surveillance.

In total, 250 ctDNA-positive patients were eligible for randomization, and at a median follow-up of 16.1 months, the primary endpoint of investigator-assessed DFS was significantly better for the 167 patients who received atezolizumab than for their 83 counterparts who received placebo.

The respective median DFS durations were 9.9 and 4.8 months, and the hazard ratio (HR) for recurrence or death was 0.64 in favor of the PD-L1 inhibitor. The 12-month DFS rates were 44.7% versus 30.0%, and the 24-month rates were 28.0% versus 12.1%.

OS was similarly significantly prolonged with the use of atezolizumab compared with placebo, at a median of 32.8 versus 21.1 months, and a HR for death of 0.59 favoring active treatment. At the 12-month mark, the OS rate was 85.1% among atezolizumab-treated patients and 70.0% among those given placebo, with corresponding rates at 24 months of 62.8% and 46.9%.

Notably, the median DFS and OS times were not reached for the 357 patients who were persistently negative for ctDNA, and the 12-month rates were 95.4% and 100%, respectively, while the 24-month rates were 88.4% and 97.1%.

Powles said that follow-up of these patients will continue as the current median follow-up of 21.8 months from cystectomy could be considered “a little short,” but he believes that these findings are “pretty reassuring from a patient’s perspective in terms of the conversation about the risk–benefit ratio.”

Alexander Wyatt (University of British Columbia, Vancouver, Canada), who discussed the presentation, said that “this is the strongest evidence to date for intervening with adjuvant systemic therapy on the basis of detecting plasma ctDNA.”

But open questions remain, he added, such as whether the effect is therapy-agnostic, and “how and when should we be testing for ctDNA in bladder cancer, and how sensitive a test should we be using.”

The IMvigor011 results appear simultaneously in The New England Journal of Medicine.

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ESMO Congress 2025; Berlin, Germany: 17–21 October
N Engl J Med 2025; doi:10.1056/NEJMoa2511885