At ASCO we presented the first results and biomarker of the SURE-01trial. This study is about patients with muscle-invasive bladder cancer which is a challenging disease. For many years the standard treatment for these patients was represented by cisplatin-based neoadjuvant chemotherapy followed by radical cystectomy. But around half of patients are not eligible for cisplatin and receive a radical cystectomy without neoadjuvant chemotherapy. For these patients the prognosis is dismal because there is a high rate of relapse so the overall survival is short.
With the SURE-01 trial we designed an alternative neoadjuvant treatment also for cisplatin-ineligible or refusing patients using sacituzumab govitecan which is a new antibody-drug conjugate targeting TROP-2.
What was the study design?
This was a single-centre phase II trial for patients with muscle-invasive bladder cancer. So patients with cT2 - T4 N0 urothelial carcinoma were treated with four cycles of neoadjuvant sacituzumab govitecan and then re-evaluated for a radical cystectomy. The primary endpoint of the study was the rate of patients achieving a complete response, that’s a ypT0N0 response rate. Among the secondary endpoints there were the event free survival, the relapse free survival, the overall survival and safety analysis.
We also presented biomarker analysis using the Decipher Bladder Cancer and ctDNA results.
What were the key findings?
We included 37 patients in the intention to treat population in a 3-year period. Sacituzumab govitecan determined a ypT0N0 response rate of around 32% so these patients after 12 months had an event free survival rate of around 75%. In patients achieving ypT0N0 responses there were no relapse events.
We also determined that in ten patients with high risk disease after the use of neoadjuvant sacituzumab in case of positive ctDNA, in 8 out of 10 patients this ctDNA became undetectable.
In the biomarker analysis we showed that, for example, the response rate was higher in patients with infiltrated luminal subtype. Regarding the expression of TROP-2, it had no prognostic value. Instead, the expression of the TOP1 gene, that is the gene encoding for TROP-2, this gene had a prognostic role.
What could be the clinical significance of these results?
The results shed light on the possibility to treat patients who are ineligible for or refusing cisplatin with neoadjuvant alternatives to chemotherapy, in this case represented by sacituzumab govitecan. Maybe in the future we will also use these drugs, we are already using these drugs to test the possibility to do a bladder-sparing approach.
