Disitamab Vedotin Plus Tislelizumab Shows Responses in Unresectable Non–Muscle-Invasive Bladder Cancer

Patients with transurethrally unresectable, very high-risk non–muscle-invasive bladder cancer who cannot undergo or decline radical cystectomy lack established nonsurgical therapy. An open-label, single-arm phase 2 trial at an academic hospital evaluated disitamab vedotin, an ERBB2-targeted antibody-drug conjugate, plus tislelizumab in 28 adults with ERBB2-positive disease. Median age was 72 years and median follow-up was 29.4 months. Treatment was administered every three weeks, with extended treatment for responders.

The primary endpoint was complete response of high-risk disease, defined as absence of high-grade tumor, T1 disease, carcinoma in situ, or progression. Responses occurred in 19 of 26 efficacy-evaluable patients (73.1%; 95% CI, 54.8%–91.3%) and 19 of all 28 treated patients (67.9%; 95% CI, 49.4%–86.3%), counting two preassessment withdrawals as nonresponders. Both analyses met the prespecified primary criterion. Among responders, the estimated 24-month sustained response was 83.5% (95% CI, 68.0%–100.0%), with no muscle-invasive or metastatic progression reported.

Treatment-related adverse events occurred in 25 patients (89.3%), most commonly paresthesia, alopecia, and pruritus. Four patients (14.3%) had grade 3–4 events, two (7.1%) discontinued treatment, and none had grade 5 events. The findings support further investigation of this nonsurgical approach, but the small, single-center, nonrandomized study cannot establish comparative benefit or replace evidence supporting cystectomy. Randomized trials are needed.