Adjuvant Atezolizumab Generates DFS, OS Benefit Regardless of Tumor Size, Nodal Status, and Prior NAC in ctDNA+ MIBC

Treatment with adjuvant atezolizumab (Tecentriq) provided disease-free survival (DFS) and overall survival (OS) benefits over placebo regardless of tumor stage, nodal status, or prior receipt of neoadjuvant chemotherapy (NAC) in patients with circulating tumor DNA (ctDNA)–positive muscle-invasive bladder cancer (MIBC) by serial testing, according to data from an exploratory subgroup analysis of the phase 3 IMvigor11 trial (NCT04660344) presented at the 26th Annual Meeting of the Society of Urologic Oncology.¹

Of note, the rates of ctDNA positivity were higher in patients with higher tumor stage or a positive nodal status at the time of cystectomy, though investigators noted that surgical staging alone was not sufficient for predicting ctDNA status.

Among patients with persistent ctDNA negativity, the risk of recurrence or death was low across all tumor stages, nodal statuses, and receipt of prior NAC following cystectomy.

“These results support the use of serial ctDNA testing after cystectomy to enhance risk determination beyond classical surgical pathological staging and identify patients with ctDNA-positive status who benefit from adjuvant atezolizumab while sparing patients who persistently test ctDNA-negative from unnecessary treatment,” Juergen E. Gschwend, MD, PhD, a professor of urology at the Technical University of Munich’s School of Medicine and Health in Germany, stated in a presentation of the data.

What did previously reported data from IMvigor011 indicate about the potential role of adjuvant atezolizumab in ctDNA-positive MIBC?

Radical cystectomy with or without neoadjuvant therapy represents a potential curative option for patients with MIBC, but patients often experience variable outcomes. Accordingly, improving the identification of patients with MIBC at a higher risk of disease recurrence is a priority. There is an increasing body of evidence supporting the prognostic value of ctDNA-based minimal residual disease (MRD) detection following cystectomy.

IMvigor011 was designed to evaluate the use of adjuvant atezolizumab in ctDNA-positive MIBC by way of serial ctDNA monitoring. Findings from the study were previously presented at the 2025 ESMO Congress and simultaneously published in the New England Journal of Medicine.² At a median follow-up of 16.1 months, patients who tested positive for ctDNA and were treated with atezolizumab (n = 167) achieved a median DFS of 9.9 months (95% CI, 7.2-12.7) vs 4.8 months (95% CI, 4.1-8.3) with placebo (n = 83), per investigator assessment (HR, 0.64; 95% CI, 0.47-0.87; P = .0047). The HR for DFS was 0.69 (95% CI, 0.48-0.91). The median OS was 32.8 months (95% CI, 27.7-not evaluable [NE]) with atezolizumab vs 21.1 months (95% CI, 14.7-NE) in the placebo arm (HR, 0.59; 95% CI, 0.39-0.90; P = .0131).

How was the IMvigor11 trial designed?

IMvigor011 enrolled patients with MIBC who underwent radical cystectomy within 6 to 24 weeks of screening and had histologically confirmed (y)pT2-T4aN0M0 or (y)pT0-T4aN+M0 urothelial cancer with no evidence of radiographic disease progression.¹ Prior neoadjuvant therapy was permitted, and an ECOG performance status of 0 to 2 was required.

Following enrollment, patients underwent serial ctDNA testing every 6 weeks and radiographic imaging every 12 weeks until 1 year post-cystectomy. If patients tested ctDNA negative, serial ctDNA testing was repeated; those who remained ctDNA negative for up to 1 year did not receive any treatment, and surveillance continued with follow-up. Patients who tested positive for ctDNA at any point without evidence of radiographic disease were randomly assigned 2:1 to receive either 1680 mg of atezolizumab or placebo once every 4 weeks for up to 1 year.

The trial’s primary end point was Investigator-assessed DFS; OS was a key secondary end point.

Of the 761 patients enrolled during the surveillance monitoring period, 379 tested positive for ctDNA at any point, and 377 patients remained in persistent ctDNA negativity. Five patients had no ctDNA results. Assessment of pathologic staging at cystectomy showed that patients had (y)pT2N0 disease, (ctDNA+, n = 48; ctDNA-negative, n = 129), including pT2N0 (n = 17; n = 66) and (y)pT2N0 (n = 31; n = 63) staging; (y)pT3-4N0 disease (n = 123; n = 171),(y)pT≤2M+ disease (n = 66; n = 45), or (y)pT3–4N+ disease (n = 141; n = 30). Corresponding ctDNA positivity rates for patients with pT2N0, (y)pT2N0, (y)pT3-4N0, (y)pT≤2M+ and (y)pT3–4N+ disease were 20.5%, 33.0%, 41.8%, 59.5% and 82.5%, respectively .The data cutoff for the current analysis was June 15, 2025, and the median follow-up from random assignment was 16.1 months.

How did DFS and OS differ according to tumor stage, nodal status, and prior NAC in the ctDNA-positive patient population?

Tumor Stage

In those with (y)p≤T2 disease:

• The median DFS was 14.8 months (95% CI, 6.6-25.1) with atezolizumab (n = 53) vs 8.4 months (95% CI, 4.2-14.6) with placebo (n = 27; unstratified HR, 0.56; 95% CI, 0.31-1.01).
• The 12- and 24-month DFS rates with atezolizumab were 54.9% and 36.2%, respectively; corresponding rates with placebo were 37.1% and NE.
• The median OS was NE (95% CI, 29.1-NE) with atezolizumab vs 27.4 months (95% CI, 20.1-NE) with placebo (unstratified HR, 0.77; 95% CI, 0.32-1.90).
• The 12- and 24-month OS rates were 91.9% and 74.0% with atezolizumab. Corresponding rates in the placebo arm were 91.8% and 60.6%.

In the (y)pT3–4 group:

• The median DFS with atezolizumab (n = 114) was 8.3 months (95% CI, 6.5-10.6) vs 4.2 months (95% CI, 3.0-6.3) with placebo (n = 56; unstratified HR, 0.64; 95% CI, 0.45-0.92).
• The 12- and 24-month DFS rates with atezolizumabwere 39.8% and 24.1%, respectively; corresponding DFS rates with placebo were 25.7% and 18.4%.
• The median OS was 29.9 (95% CI, 21.1-NE) with atezolizumab vs 13.1 months (95% CI, 10.5-NE) with placebo (unstratified HR, 0.58; 95% CI, 0.37-0.93).
• The 12- and 24-month OS rates were 81.9% and 57.4% with atezolizumab. Corresponding rates in the placebo arm were 58.3% and 40.0%.

Nodal Status

In patients with (y)pN0 disease:

• The median DFS was 8.3 months (95% CI, 4.5-13.2) with atezolizumab (n = 71) vs 6.2 months (95% CI, 2.3-10.6) with placebo (n = 35; unstratified HR, 0.74; 95% CI, 0.45-1.12).
• The 12- and 24-month DFS rates in the atezolizumab arm were 42.5% and 25.2%, respectively; corresponding DFS rates with placebo were 30.6% and 10.2%.
• The median OS was 29.9 months (95% CI, 21.1-NE) with atezolizumab vs 18.1 (95% CI, 12.1-NE) with placebo (unstratified HR, 0.72; 95% CI, 0.38-1.39).
• The 12- and 24-month OS rates in the atezolizumab arm were 81.2% and 55.4%, respectively. Corresponding OS rates with placebo were 69.2% and 43.9%.

In the (y)pN+ population:

• The median DFS was 10.4 months (95% CI, 7.1-19.5) with atezolizumab (n = 96) and 4.8 months (95% CI, 4.1-8.3) with placebo (n = 48; unstratified HR, 0.58; 95% CI, 0.39-0.86).
• The 12- and 24-month DFS rates in the atezolizumab arm were 46.4% and 30.0%, respectively; corresponding DFS rates with placebo were 28.6% and 13.4%.
• The median OS was 34.4 months (95% CI, 29.1-NE) with atezolizumab vs 22.2 months (95% CI, 17.4-NE) with placebo (unstratified HR, 0.61; 95% CI, 0.36-1.05).
• The 12- and 24-month OS rates in the atezolizumab arm were 87.8% and 67.8%, respectively. Corresponding OS rates with placebo were 70.9% and 48.4%.

Prior NAC

In patients with no prior exposure to NAC:

• The median DFS was 10.5 months (95% CI, 6.6-14.5) with atezolizumab (n = 87) and 5.3 months (95% CI, 2.3-9.7) with placebo (n = 50; unstratified HR, 0.66; 95% CI, 0.44-1.00).
• The 12- and 24-month DFS rates in the atezolizumab arm were 45.1% and 28.1%, respectively; corresponding DFS rates with placebo were 34.9% and 16.4%.
• The median OS was 35.9 months (95% CI, 24.4-NE) with atezolizumab vs 18.2 months (95% CI, 13.1-NE) with placebo (unstratified HR, 0.52; 95% CI, 0.31-0.89).
• The 12- and 24-month OS rates in the atezolizumab arm were 89.0% and 65.5%, respectively. Corresponding OS rates with placebo were 66.5% and 43.9%.

In patients who had received prior NAC:

• The median DFS was 8.2 months (95% CI, 6.1-12.8) with atezolizumab (n = 80) and 4.4 months (95% CI, 3.7-10.4) with placebo (n = 33; unstratified HR, 0.59; 95% CI, 0.37-0.95).
• The 12- and 24-month DFS rates in the atezolizumab arm were 44.5% and 28.1%, respectively; corresponding DFS rates with placebo were 20.1% and 5.0%.
• The median OS was 30.8 months (95% CI, 22.0-NE) with atezolizumab vs NE (95% CI, 14.7-NE) with placebo (unstratified HR, 1.00; 95% CI, 0.50-1.99).
• The 12- and 24-month OS rates in the atezolizumab arm were 80.5% and 69.9%, respectively. Corresponding OS rates with placebo were 75.7% and 53.3%.

What were the DFS and OS outcomes with adjuvant atezolizumab according to tumor stage, nodal status, and prior NAC in patients with persistent ctDNA negativity?

Efficacy outcomes according to tumor stage were as follows:

• In the (y)p≤T2 population (n = 166), 12- and 24-month DFS rates were 96.3% and 89.1%, respectively; the 12- and 24-month OS rates were 100% and 97.3%
• In the (y)pT3–4 population (n = 189), corresponding DFS rates were 94.6% and 87.5%; corresponding OS rates were 100% and 96.9%.

When assessed by nodal status:

• In the (y)pN0 population (n = 285), 12- and 24-month DFS rates were 96.4% and 89.3%, respectively; the 12- and 24-month OS rates were 100% and 96.7%.
• In the (y)pN+ population (n = 72), corresponding DFS rates were 91.5% and 84.5%; corresponding OS rates were 100% and 98.4%

DFS and OS rates according to receipt of prior NAC were as follows:

• Among patients with no prior receipt of NAC (n = 189), 12- and 24-month DFS rates were 96.2% and 86.2%, respectively; the 12- and 24-month OS rates were 100% and 95.7%, respectively.
• For those who previously received NAC (n = 168), corresponding DFS rates were 94.6% and 90.8%; corresponding OS rates were 100% and 98.6%, respectively.

References

1. Gschwend JE, Bellmunt J, Arslan C, et al. Circulating tumor DNA-guided adjuvant atezolizumab vs placebo in patients with muscle-invasive bladder cancer after radical cystectomy: exploratory subgroup analysis of the phase 3 IMvigor011 trial. Presented at: 26th Annual Meeting of the Society of Urologic Oncology. December 2-5, 2025; Phoenix, Arizona.
2. Powles T, Kann AG, Castellano D, et al. ctDNA-guided adjuvant atezolizumab in muscle-invasive bladder cancer. N Engl J Med. Published online October 20, 2025. doi:10.1056/NEJMoa2511885