IMvigor011 Exploratory Analysis Reveals OS, DFS Rates of ctDNA-Negative Patients With MIBC

At the 25th Annual Meeting of the Society of Urologic Oncology, an exploratory analysis of the phase III IMvigor011 trial’s surveillance cohort has provided new data on the disease-free survival (DFS) and overall survival (OS) rates of patients with high-risk muscle-invasive bladder cancer (HR MIBC) who have continual circulating tumor DNA (ctDNA)-negative biomarker status after undergoing cystectomy.

IMvigor011 compared the efficacy of atezolizumab with placebo in patients with HR MIBC who remained ctDNA-positive post-cystectomy using Signatera, a tumor-informed molecular residual disease test developed by Natera.

The trial enrolled patients into a surveillance run-in phase 6 to 24 weeks after cystectomy. Each patient underwent serial ctDNA testing every 6 weeks for 6 months, then every 12 weeks for up to 12 months, as well as imaging every 12 weeks up to 12 months.

Patients who remained ctDNA-negative after 12 months continued imaging and follow-up for DFS and OS, while eligible patients who became ctDNA-positive were randomized to receive either atezolizumab or placebo.

The exploratory analysis focused on outcomes in patients from the surveillance cohort who were persistently ctDNA-negative. A total of 286 patients who were ctDNA-negative after cystectomy were enrolled, and 171 patients met the criteria to be included in the analysis. The tumor stage distribution was 10.7% <T2, 34.9% T2, 43.8% T3 and 10.7% T4.

A total of 51.5% of patients did not receive neoadjuvant chemotherapy. At a median follow-up of 16.3 months (IQR, 11.6-19.3), 17 patients (9.9%) experienced a DFS event. The 12- and 18-month DFS rates were 92% and 88%, respectively, and DFS outcomes were similar regardless of PD-L1 status and tumor stage at cystectomy. With an OS event rate of 1.2%, the 12-month OS rate was 100%, and the 18-month OS rate was 98%.

This exploratory analysis of the phase III IMvigor011 trial has demonstrated that serial ctDNA testing may serve as a better risk stratification tool than landmark ctDNA testing in patients with HR MIBC after cystectomy.