A ctDNA-guided atezolizumab therapy in bladder cancer

Data from IMvigor011 phase 3 trial, recently published on The New England Journal of Medicine, showed that a ctDNA-guided adjuvant therapy with atezo­liz­u­mab led to significantly longer disease-free survival and overall survival than placebo in patients with muscle-invasive bladder cancer.

For the IMvigor011 trial, a total of 761 patients with muscle-invasive bladder cancer and no radiographic evidence of disease after surgery were enrolled and tested for ctDNA during surveillance, to detect molecular residual disease that may identify patients at high risk for recurrence after cystectomy who can benefit from adjuvant immunotherapy. Patients who tested ctDNA-positive underwent randomization, 167 to the atezo­liz­u­mab group and 83 to the placebo

group. The median disease-free survival was 9.9 months with atezo­liz­u­mab and 4.8 months with placebo, the median overall survival was 32.8 months and 21.1 months respectively. Among 357 patients with persistent ctDNA-negative status, disease-free survival was 95% at the end of the 1-year monitoring period and 88% at 2 years. Atezo­lizumab treatment was not associated with any new safety signals. As authors conclude, «Results from the IMvigor011 trial indicate that serial

ctDNA-based monitoring of molecular residual disease can identify patients with bladder cancer who may benefit from adjuvant atezolizumab while sparing patients who persistently test ctDNA-negative from unnecessary treatment, toxicity, and costs. These findings support the clinical usefulness of ctDNA-based testing for molecular residual disease in guiding adjuvant treatment decisions for bladder cancer and may have implications for other solid tumors with heterogeneous outcomes after curative-intent surgery».