Game-changing roles: ctDNA and adjuvant NIVO in advanced BCa treatment
The Game-changing Session “Prime time for adjuvant treatment in locally advanced bladder cancer” led by Prof. Morgan Rouprêt (FR) and Dr. Jochen Walz (FR) featured two lectures on the IMvigor011 and CheckMate 274 studies, which were presented by Prof. Thomas Powles (GB) and Prof. Matthew Galsky (US), respectively.
Serial ctDNA testing: A risk-stratification tool
In “Clinical outcomes in patients with high-risk, post-cystectomy muscle-invasive bladder cancer (MIBC) with persistent circulating tumour DNA-negative (ctDNA-) status on serial testing: surveillance analysis from the IMvigor011 study”, Prof. Powles underscored that the analysis suggests that serial ctDNA testing may have greater clinical utility than landmark ctDNA testing as a risk-stratification tool.
The data led to increasing confidence that patients with high-risk MIBC who have persistent ctDNA- status after cystectomy may be spared from adjuvant treatment. “A key question for us as a group is can we spare these patients adjuvant treatment? We know immune checkpoint inhibition is associated with a 10% chance of life-changing toxicity and treating patients with a small risk of relapse and death is a question we will need to address,” said Prof. Powles.
The analysis was limited to ctDNA- patients and suggests that ctDNA status is selected for patients with favourable clinical prognosis regardless of PD-L1 status and pathologic staging at cystectomy.
About the study
IMvigor011 is a global, double-blind, randomised phase III study that assesses the efficacy of atezolizumab (anti-PD-L1) versus placebo (PBO) in patients with high-risk MIBC and who are ctDNA+ post-cystectomy.
The trial enrolment is still ongoing. The trial participants must be patients with high-risk MIBC who had cystectomy within the timeframe of six to 24 weeks with no evidence of residual disease. The process will involve plasma collection and imaging. Participants will be classified as either ctDNA+ or ctDNA-. ctDNA+ patients will either receive atezolizumab or placebo (PBO) The primary endpoint is investigator-assessed disease-free survival (DFS). ctDNA- patients will be under surveillance.
Adjuvant nivolumab (NIVO) benefits
CheckMate 274 is a randomised phase III study that enrolled patients with muscle-invasive urothelial cancer (MIUC) who are at high risk for recurrence after radical surgery. The patients were randomised to receive a placebo or adjuvant nivolumab (NIVO). The study met its primary endpoints: adjuvant NIVO improved DFS versus PBO in the intention-to-treat (ITT) population and in patients with tumour PD-L1 expression.
Updates
During “Extended follow-up from CheckMate 274 including the first report of overall survival outcomes”, Prof. Galsky concluded that with extended follow-up in CheckMate 274, adjuvant NIVO continued to show DFS, non-urothelial tract recurrence-free survival (NUTRFS), and distant metastasis-free survival (DMFS) benefits versus PBO in both ITT and PD-L1 ≥ 1% populations.
Overall survival (OS) data from interim analyses favoured adjuvant NIVO over PBO showed that in the ITT population, median OS reached 69.5 months with NIVO versus 50.1 months with PBO (hazard ratio [HR] 95%Cl, 0.76 [0.61-0.96]).
Furthermore, in the PD-L1 ≥ 1% population, median OS was not reached with either treatment (HR [95%Cl]), 0.56 [0.36-0.86]); 36-months OS rates were 71.3% with NIVO versus 56.6% with PBO. There was a trend for OS benefit with NIVO among prespecified subgroups of ITT patients.
Prof. Galsky stated that continued follow-up of OS is ongoing and no new safety signals were identified since the previous analysis.
The results provide additional support for adjuvant NIVO as a standard of care for high-risk MIUC after radical resection, potentially providing an opportunity for a curative outcome.