Multinational phase 2 trial of neoadjuvant sacituzumab govitecan for muscle-invasive bladder cancer

The multinational phase 2 SURE-01 trial evaluated neoadjuvant sacituzumab govitecan (SG) followed by radical cystectomy (RC) in patients with muscle-invasive bladder cancer (MIBC) who are ineligible for or refuse neoadjuvant chemotherapy. Eligible patients were adults with cT2-T4aN0M0 MIBC and an ECOG performance status 0 or 1. Patients received four 3-week cycles of SG 10 mg/kg on day 1 and day 8, followed by RC. The primary endpoint was pathologic complete response (pCR; pT0N0) rate. After the initial eight of 44 patients were enrolled, the protocol was amended with a SG dose of 7.5 mg/kg, with primary prophylaxis for neutropenia, due to the occurrence of two deaths (one treatment-related). Subsequent grade 3-4 treatment related adverse events occurred in 5 patients (13.9%). Fourteen patients (31.8%) refused to undergo RC, accounting for 12 repeating a transurethral resection of the bladder tumor and two undergoing active surveillance. The median follow-up was 22 months (IQR 15-26). In the intention-to-treat population the ypT0N0 rate was 9.1% (95% CI 2.5-21.7) and the overall ypT0N0-x rate was 29.5% (16.7-45.2), with an enrichment of ypT0 responses in nonluminal subtypes (46% versus 14% of luminal). The 24-months event-free survival rate was 71.4% (95% CI 58-87.8), with longer EFS for participants with lower TOP1-expressing tumors. The authors conclude that neoadjuvant SG at the reduced dose of 7.5 mg/kg, was active with a manageable safety profile, corroborating TROP2 as a suitable target in MIBC.