Disitamab vedotin plus PD-1 inhibitors as neoadjuvant therapy for cisplatin-ineligible muscle-invasive bladder cancer: A real-world retrospective study.

Abstract

691 Background: Cisplatin-based neoadjuvant chemotherapy (NAC) remains the standard for muscle-invasive bladder cancer (MIBC), improving 5-year overall survival by about 8%. However, many patients with renal impairment or poor performance status cannot tolerate cisplatin. Disitamab Vedotin (DV), a HER2-targeted antibody–drug conjugate, has shown encouraging efficacy and safety in metastatic urothelial carcinoma. This study evaluated the efficacy of DV combined with PD-1 inhibitors as NAC in cisplatin-ineligible MIBC. Methods: We retrospectively analyzed 40 patients with pathologically or radiologically confirmed MIBC (T2–4N0–1M0) who were ineligible for cisplatin due to renal dysfunction or chemotherapy intolerance. Treatment regimens included DV (2 mg/kg every 2 weeks) plus pembrolizumab, tislelizumab (200 mg every 3 weeks), or toripalimab (3 mg/kg every 3 weeks). Primary endpoints were pathological complete response (pCR) and clinical complete response (cCR); the secondary endpoint was disease-free survival (DFS). Results: Among 40 enrolled patients (70% male), HER2 IHC was 1+ in 1 case (2.5%), 2+ in 20 (50%), and 3+ in 19 (47.5%). The median number of DV cycles was 5 (range 4–6). After NAC, 27 patients underwent radical cystectomy (RC), and 13 received bladder-preserving therapy. pCR was achieved in 10/27 RC patients (37.0%), and cCR in 10/13 bladder-preserving patients (76.9%), yielding a total CR rate of 50%. The 1-year DFS rate was 95%. Conclusions: DV combined with PD-1 inhibitors as neoadjuvant therapy showed high complete response rates and favorable short-term survival in cisplatin-ineligible MIBC. This regimen may offer an effective and bladder-sparing therapeutic alternative for patients unfit for standard cisplatin-based chemotherapy.