Neoadjuvant sacituzumab govitecan shows promising activity in muscle-invasive urothelial bladder cancer
Dr Antonio Cigliola - IRCCS San Raffaele Hospital, Milan, Italy

In our abstract we presented the preliminary results of the SURE-01 study with perioperative sacituzumab govitecan in patients with muscle-invasive bladder cancer. In particular, the prognosis of patients who have muscle-invasive bladder cancer and are ineligible to receive cisplatin-based chemotherapy remains poor. For these patients upfront radical cystectomy or chemoradiation remain the standards of care.

In this trial we used neoadjuvant sacituzumab govitecan, four cycles of this drug, and then patients underwent radical cystectomy. The primary endpoint was pathological complete response rate while secondary endpoints were pathologic downstaging rate, EFS, OS and quality of life. We reported the pathological findings of 21 patients. Of these 21 patients 18 completed all four cycles of neoadjuvant sacituzumab govitecan while three patients died during the neoadjuvant treatment. The protocol was amended after the initial eight patients due to several cases of G3/4 adverse events, in particular diarrhoea and neutropenia, and two deaths, one treatment-related and one unrelated. 

Overall after the amendment treatment was well tolerated with G3 adverse events present in 33.3% of patients and G4 in 19.1% of patients. The most common adverse G3/4 adverse events were neutropenia and diarrhoea.

Considering the activity, the efficacy of the treatment, 18 patients received surgery, seven of them refused radical cystectomy and underwent reTURBT after the evidence of a clinical complete response. So considering the radical cystectomy evaluable patients pathological complete response rate was 36.4% while considering that in the intention to treat population with the patients who received radical cystectomy or reTURBT pathological complete response rate was 47.6% with a pathological downstaging in 11 patients. Another interesting finding was that patients with high risk residual disease revealed a ctDNA negative after radical cystectomy.

So the conclusion is that after the amendment treatment with sacituzumab govitecan is safe and the activity of sacituzumab govitecan in this setting is high. So this data supports the use of sacituzumab in this setting.

What could be the impact of this research?

Probably in the future we can consider the use of sacituzumab govitecan in this setting, in muscle-invasive bladder cancer. Probably we will start from the dosage of 7.5mg/kg and then we can consider to use the dosage which usually is used in other types of cancers of 10mg/kg for patients who tolerate it after the first cycle of treatment. Because we know that most adverse events occurred after the first cycle.