In an Italian phase II trial (SURE-01) reported in the Journal of Clinical Oncology, Necchi et al found that neoadjuvant sacituzumab govitecan was active in patients with muscle-invasive bladder cancer (MIBC) who were ineligible for or elected not to receive neoadjuvant chemotherapy.
Study Details
In the multicenter study, 44 patients enrolled between March 2022 and July 2025 with confirmed cT2-T4aN0M0 MIBC scheduled for radical cystectomy received four cycles of sacituzumab govitecan at 10 mg/kg on days 1 and 8, once every 3 weeks, followed by surgery. The protocol was amended to use of sacituzumab govitecan at 7.5 mg/kg with primary prophylaxis for neutropenia after enrollment of the initial eight patients, due to the occurrence of two deaths (one treatment-related). The primary outcome measure was pathologic complete response.
Key Findings
A total of 14 patients (31.8%) refused to undergo radical cystectomy, with 12 undergoing repeat transurethral resection of the bladder tumor and 2 undergoing active surveillance.
Median follow-up was 22 months (interquartile range = 15–26 months). In the intent-to-treat population, the protocol-defined ypT0N0 rate was 9.1% (95% confidence interval [CI] = 2.5%–21.7%); however, the overall ypT0N0-x rate was 29.5% (95% CI = 16.7%–45.2%), with an increase in ypT0 responses among patients with nonluminal subtypes vs luminal subtypes (46% vs 14%).
The 24-month event-free survival rate was 71.4% (95% CI = 58%–87.8%), with higher rates in patients with lower TOP1-expressing tumors (P = .04). Overall survival at 24 months was 80.2% (95% CI = 67.7%–95%).
In the eight patients treated at 10 mg/kg, treatment-related grade 3 or 4 neutropenia occurred in six patients (75%) and grade 3 or 4 diarrhea occurred in four patients (50%). All severe events occurred after cycle 1, day 8. There were two deaths, one of which was treatment-related (septic shock). Among 36 patients receiving the reduced dose, grade 3 or 4 treatment-related adverse events consisted of neutropenia in two patients (5.6%) and diarrhea in one patient (2.8%).
The investigators concluded: “Neoadjuvant sacituzumab govitecan, at the reduced dose of 7.5 mg/kg, was active with a manageable safety profile, corroborating TROP2 as a suitable target for MIBC.”
Andrea Necchi, MD, of the Department of Medical Oncology, IRCCS San Raffaele Hospital, Comprehensive Cancer Center, Milan, Italy, is the corresponding author for the Journal of Clinical Oncology article.
DISCLOSURE: The study was supported by Gilead Sciences Inc. For full disclosures of the study authors, visit ascopubs.org.
