Patient-reported outcomes from IMvigor011: A phase 3 study of circulating tumor (ct)DNA–guided adjuvant atezolizumab vs placebo in muscle-invasive bladder cancer (MIBC).

4627 Background: IMvigor011 (NCT04660344) showed that serial ctDNA-based molecular residual disease (MRD) monitoring can identify patients (pts) with MIBC at very high risk of recurrence who benefit from adjuvant atezolizumab (atezo), demonstrating statistically significant and clinically meaningful improvements in DFS and OS vs placebo (pbo) in pts who tested ctDNA+. Pts who persistently tested ctDNA− had low risk of recurrence or death without adjuvant treatment (tx; Powles NEJM 2025). Here we report pt-reported outcomes (PROs). Methods: Pts with MIBC and no radiographic disease were enrolled and underwent serial ctDNA monitoring for up to 1 year after cystectomy; pts who tested ctDNA+ and remained disease-free were randomized to atezo or pbo every 4 weeks (wk) for 12 cycles or up to 1 year. PROs were assessed on Day (D)1 of Cycle (C)1, C3, C5, C7, C9, and C11, and at tx discontinuation. Time to confirmed deterioration (TTCD) analysis of physical functioning (PF), role functioning (RF), and global health status/quality of life (GHS/QoL) were secondary endpoints. Symptoms, functioning, and GHS/QoL per EORTC QLQ-C30, and tx side-effect burden per EORTC IL46, were exploratory endpoints. Relevant adverse events (AEs) were graded per NCI CTCAE v5. Results: Eligible pts who tested ctDNA+ (n=250) were randomized to atezo (n=167) or pbo (n=83). QLQ-C30 completion was >94% at C1D1 and >87% during tx, and >72% and >90%, respectively, for IL46. C1D1 completion rates were similar between arms. TTCD in PF, RF, and GHS/QoL showed no evidence of a difference between arms (Table). There was no clinically meaningful difference in mean change from C1D1 in symptoms, functioning, and GHS/QoL over time through C11D1 and between arms. From C1D1 to C11D1, >90% of pts reported little or no tx side-effect burden in both arms. Relevant safety data showed consistency between AEs and PROs. Conclusions: ctDNA-guided adjuvant atezo provided clinically meaningful DFS and OS benefit without negatively impacting pt-reported QoL. Clinical trial information: NCT04660344 . Atezo(n=167) Pbo(n=83) Stratified HR a (95% CI) QLQ-C30, median TTCD b (95% CI), mo PF 25.1 (18.5, NE) NE (19.4, NE) 1.25 (0.76, 2.07) RF 18.5 (12.2, NE) NE (19.4, NE) 1.45 (0.88, 2.40) GHS/QoL 35.4 (19.3, NE) 16.5 (10.9, NE) 0.71 (0.45, 1.12) IL46 tx side-effect burden, % of pts Atezo C1D1 (n=131) Atezo C11D1 (n=60) Pbo C1D1 (n=60) Pbo C11D1 (n=22) Not at all/a little 93.9 98.3 98.3 95.5 Quite a bit 6.1 1.7 1.7 4.5 Very much 0 0 0 0 a Stratification factors: Nodal status (+ vs –); tumor stage (≤pT2 vs pT3/4); programmed death ligand-1 status (<5% vs ≥5% of immune cells); time from cystectomy to first ctDNA+ sample (≤20 vs >20 wk). b Time from randomization to first clinically meaningful deterioration (≥10-point decrease) at either: ≥2 consecutive visits; or at 1 visit followed by death due to cancer progression ≤8 wk from last deteriorated PRO visit. NE, not evaluable.