Daniel P. Petrylak, MD, on Urothelial Cancer: Phase II Trial Analysis of Sacituzumab Govitecan-hziy in Metastatic Disease

The treatment of metastatic urothelial carcinoma has evolved over the past 10 years and really has come a long way. Around 2010, if a patient had metastatic bladder cancer, there were two options for platinum eligible patients, those included the MVAC chemotherapy regimen as well as gemcitabine and cisplatinum. Carboplatinum and gemcitabine was considered a standard of care for those patients who were not eligible to receive cisplatin based chemotherapy. Unfortunately, once a patient progressed after any of these regimens, the median survival was about six months. With the use of checkpoint inhibition therapy, as well as the ADCs or the antibody drug conjugates that are showing significant activity in urothelial carcinoma, we've been able to treat patients that have been otherwise refractory to treatment. So we do need more treatments for the treatment of refractory urothelial carcinoma, as well as platinum ineligible urothelial carcinoma. And that was the point of the second group of the TROPHY study. So we took patients who were ineligible to receive cisplatinum and treated those patients with Sacituzumab govitecan. We found that the response rate was 32% in all patients treated. Additionally, we found that in those patients who did not receive either prior chemotherapy or enfortumab vedotin, that the response rate was more than 50%. The toxicities that we observed with this study included neutropenia as well as diarrhea, and these were consistent with what was reported with the first cohort of the TROPHY study. So in summary, Sacituzumab govitecan has activity in platinum ineligible urothelial carcinoma, and further studies are being performed to look at the combination of Sacituzumab with checkpoint inhibition therapy. Additionally, there are studies that are ongoing with Sacituzumab combined with cisplatin in cisplatinum eligible patients. So this drug can form the core for the development of future therapies for refractory, as well as first line urothelial carcinoma.