Circulating Tumor DNA-Guided Adjuvant Atezolizumab Significantly Improves Survival Otucomes in Bladder Cancer
Results from a primary analysis of the phase 3 IMvigor011 trial reveal adjuvant atezolizumab guided by circulating tumor DNA (ctDNA) status yields significantly improved survival compared to placebo among patients with high-risk muscle-invasive bladder cancer.
These findings were reported by Thomas Powles, MD, Barts Cancer Institute, London, United Kingdom, at the 2025 European Society of Medical Oncology (ESMO) Annual Meeting in Berlin, Germany.
This trial enrolled 761 patients with high-risk muscle-invasive bladder cancer who had no radiographic evidence of disease and entered surveillance within 6 to 24 weeks after cystectomy to undergo serial ctDNA monitoring for up to 1-year post-radical cystectomy. Patients who tested ctDNA-positive (n = 250) were randomized 2:1 to receive either 1680 mg of atezolizumab (n = 167) or placebo (n = 83) every 4 weeks for up to 12 cycles for up to 1 year. Patients who persistently tested ctDNA-negative (n = 357) received no adjuvant therapy.
The primary trial end point was disease-free survival (DFS). Key secondary end points included overall survival (OS) and safety.
At a median follow-up of 16.1 months, median DFS was 9.9 months in the atezolizumab arm and 4.8 months in the placebo arm (hazard ratio [HR], 0.64; 95% confidence interval [CI], 0.47 to 0.87; P = .0047). The 12-month DFS rates were 44.7% and 29.6%, respectively. Median OS was 32.8 months in the atezolizumab arm and 21.1 months in the placebo arm (HR, 0.59; 95% CI, 0.39 to 0.90; P = .0131). The 12-month OS rates were 85.1% and 70%, respectively.
Grade 3/4 treatment-related adverse events occurred in 7.3% of patients in the atezolizumab arm and 3.6% of patients in the placebo arm. Fatal treatment-related adverse events occurred in 1.8% of patients in the atezolizumab arm. In patients who persistently tested ctDNA-negative the DFS rate was 95.4% at the end of the 1-year monitoring period and 88.4% at 2 years.
“ctDNA-guided adjuvant [atezolizumab] showed statistically significant and clinically meaningful DFS and OS improvements vs placebo,” stated Dr Powles and coauthors. “The [atezolizumab] safety profile was tolerable, with no new findings,” suggesting that ctDNA monitoring could help identify which patients can safely avoid adjuvant therapy.
Source:
Powles T, Kann A, Castellano Gauna DE, et al. IMvigor011: A phase III trial of circulating tumour (ct)DNA-guided adjuvant atezolizumab vs placebo in muscle-invasive bladder cancer. Presented at the 2025 ESMO Congress. October 17-21, 2025; Berlin, Germany. LBA8
