Sacituzumab Combo Shows Promise in Bladder Preservation Trial

Findings from the phase 2 SURE-02 trial (NCT05535218) suggest that the combination of sacituzumab govitecan-hziy (Trodelvy) and pembrolizumab (Keytruda) may offer oncologists an organ-sparing strategy to treat patients with muscle-invasive bladder cancer (MIBC). Radical cystectomy preceded by chemotherapy is the established standard of care, yet approximately half of those patients diagnosed are either too frail to tolerate the chemotherapy or refuse it, leaving them with limited options.

Investigators enrolled 49 patients with MIBC who were ineligible for or declined the standard cisplatin-based chemotherapy. These patients, with a median age of 66 years (IQR, 61-71), were treated with a combination of pembrolizumab and sacituzumab govitecan.

After 4 cycles of this dual therapy, patients did not automatically proceed to surgery. Instead, the treatment plan was reevaluated, and patients were offered either a radical cystectomy or a more conservative transurethral resection of the bladder tumor (re-TURBT) if they wished to avoid bladder removal. This was followed by 13 cycles of adjuvant pembrolizumab.

After a median follow-up of 14 months, 39% of patients (19/49) achieved a clinical complete response. This stringent measure required negative imaging and, crucially, no evidence of viable cancer being found during the re-TURBT procedure.

All 19 of those patients successfully avoided radical cystectomy. Furthermore, every patient who achieved this clinical complete response remained metastasis-free. Investigators reported that 2 of these patients later experienced an intravesical relapse. The finding suggests that for a substantial portion of patients, the bladder can be preserved without compromising systemic control of the disease.

Sixty-three patients were screened; 49 patients were enrolled, treated, and evaluated for safety and efficacy. The majority were male (84%) and White (98%). Thirty-three patients (67%) had a cT2 stage tumor, and 21 (43%) had a centrally confirmed variant histology.

Trial Details

Patients received 4 cycles of intravenous pembrolizumab 200 mg on day 1 and intravenous sacituzumab govitecan 7.5 mg/kg on days 1 and 8, every 3 weeks, followed by radical cystectomy or re-TURBT and 13 cycles of postsurgical pembrolizumab at 200 mg every 3 weeks. The primary end point was clinical response rate, defined as negative imaging and no viable tumor at re-TURBT in patients not undergoing radical cystectomy.

The regimen’s safety profile was also notable. Although 8 patients, or 16%, experienced grade 3 treatment-related adverse events, with diarrhea being the most common, there were no grade 4 or 5 adverse events and no treatment-related deaths. Serious adverse events were reported in 3 patients, including 2 cases of bullous pemphigoid and 1 case of colitis.

The researchers concluded that the combination of sacituzumab govitecan and pembrolizumab in the perioperative setting yields a promising clinical complete response rate. For almost 40% of the patients in this study, this approach facilitated bladder preservation with sustained remission, offering a potential alternative to the traditional pathway of radical surgery and chemotherapy. These findings will likely fuel further investigation into organ-sparing strategies for this difficult-to-treat cancer.

REFERENCE

Necchi A, Maiorano BA, deJong JJ, et al. Neoadjuvant sacituzumab govitecan plus pembrolizumab, followed by adjuvant pembrolizumab, in patients with muscle-invasive bladder cancer (SURE-02): a single-arm, phase 2 study. Lancet Oncol. Published online February 27, 2026. doi:10.1016/S1470-2045(26)00050-1