Can MRD Assessment with ctDNA in Muscle Invasive Bladder Cancer Improve Outcomes
by Dr. C.H. Weaver M.D. 4/7/2021
Bladder cancer patients with residual cancer following surgery are known to be at the highest risk of recurrence, and patients without residual disease are less likely to benefit from additional treatment. A test that could accurately identify the presence of minimal residual disease (MRD) and predict who benefits and who could avoid unnecessary therapy would be of great value. Several MRD tests are about to become available. The Signatera MRD test is one such test and is unique in that it is personalized.
Muscle invasive bladder cancer carries a substantial risk of recurrence and/or death because nearly 50 percent of patients develop recurrence within two years of cystectomy (the surgery to remove the bladder). Patients with muscle invasive urothelial (bladder) cancer and evidence of circulating cancer cell DNA (ctDNA) following surgical removal of visible cancer are known to have high risk of disease recurrence following cystectomy. However, these patients experience improved clinical outcomes when treated with adjuvant Tecentriq® (atezolizumab) immunotherapy when compared to patients undergoing observation, according to results from the IMvigor010 clinical trial presented at the European Medical Oncology Society Annual Meeting in December 2020**.** (1,2)
Researchers evaluated ctDNA data from patients with muscle invasive bladder cancer enrolled in the Phase III IMvigor010 clinical trial using the Natera™ Signatera™ assay using blood samples obtained at a median of 11 weeks following surgery in 581patients.
Thirty-seven percent of patients were determined to be ctDNA-positive, and the study found an association between ctDNA-positive patients and survival without cancer recurrence in Tecentriq treated patients compared to patients undergoing observation without adjuvant therapy. The overall survival of ctDNA-positive patients treated with Tecentriq was 26 months compared to 16 months with observation. Patients who were ctDNA-negative did not benefit from Tecentriq treatment when compared to those undergoing observation.
The study authors concluded that these findings demonstrate that post-surgical ctDNA positivity can identify which patients with muscle invasive bladder cancer are likely to benefit from adjuvant Tecentriq immunotherapy.
A confirmatory clinical trial, “A Study of Atezolizumab Versus Placebo as Adjuvant Therapy in Patients With High-Risk Muscle-Invasive Bladder Cancer Who Are ctDNA Positive Following Cystectomy (IMvigor011)” ) is ongoing. The trial evaluates whether adjuvant Tecentriq immunotherapy provides benefit in patients with PD-L1-positive, muscle invasive bladder cancer who are MRD-positive within 20 weeks post-surgery based on Natera's ctDNA test.
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Powles T, Assaf ZJ, Davarpanah N, et al. Clinical outcomes in post-operative ctDNA-positive muscle-invasive urothelial carcinoma (MIUC) patients after atezolizumab adjuvant therapy. ESMO Immuno-Oncology Virtual Congress 2020