Phase 2 trial of neoadjuvant sacituzumab govitecan plus pembrolizumab, followed by adjuvant pembrolizumab for muscle-invasive bladder cancer

Standard-of-care treatment for muscle-invasive bladder cancer (MIBC) is neoadjuvant chemotherapy followed by radical cystectomy; however, approximately 50% of patients are ineligible for or refuse neoadjuvant chemotherapy. The phase 2 SURE-02 study, at IRCCS San Raffaele Hospital (Milan, Italy) evaluated neoadjuvant sacitumumab govitecan (SG) plus pembrolizumab and adjuvant pembrolizumab, within a bladder-sparing approach. The study included adult patients with an ECOG performance status 0 or 1 and newly diagnosed MIBC (stage cT2-T3bN0M0) who were deemed ineligible for or declined cisplatin-based neoadjuvant chemotherapy, and were scheduled for radical cystectomy. Patients received four cycles of pembrolizumab plus SG, followed by radical cystectomy or redo-transurethral resection of the bladder tumor (re-TURBT), and 13 cycles of postsurgical pembrolizumab. The primary endpoint was clinical complete response rate. Forty-nine patients were treated. After a median follow-up of 14 months (IQR 8-18), 19 patients (39%; 95% CI 25-54) had a clinical complete response; all of whom underwent a re-TURBT. All patients with clinical complete response were metastasis-free; two patients developed an intravesical relapse. Grade 3 treatment-related adverse events occurred in eight patients (16%); there were no grade 4 or 5 TRAEs. The authors conclude that perioperative SG plus pembrolizumab revealed a promising clinical complete response rate, without the occurrence of grade 4 or 5 adverse events, allowing bladder preservation with sustained remission in approximately 40% of patients.