Efficacy and safety of neoadjuvant therapy with disitamab vedotin plus toripalimab in treating muscle invasive urothelial bladder cancer followed by selective bladder-preserving or radical cystectomy.

e16590 Background: Neoadjuvant cisplatin-based chemotherapy remains the standard systemic therapy for cisplatin-eligible patients undergoing radical cystectomy (RC) for muscle-invasive bladder cancer (MIBC). However, its application is constrained due to suboptimal efficacy and considerable safety concerns. The combination of immunotherapy with antibody-drug conjugates is being actively explored as an innovative approach to neoadjuvant therapy for MIBC. Disitamab vedotin (DV) has demonstrated encouraging outcomes in HER2-positive locally advanced or metastatic urothelial carcinoma. Thereby our study aimed to assess the effectiveness and safety of DV combined with toripalimab (PD-1 inhibitor) as neoadjuvant therapy in patients with HER2-expressing MIBC followed by either selective bladder preservation or RC. Methods: This retrospective, single-arm study included patients with histopathologically diagnosed MIBC (T2-4N0-1M0). The regimens comprised DV at a dose of 2.0 mg/kg and toripalimab at 3.0 mg/kg, both delivered intravenously biweekly. Following the neoadjuvant therapy, patients achieving a complete response (CR) or downstaged to non-MIBC were given the choice of either RC or opting for bladder-sparing. Patients not meeting the criteria underwent RC. The primary endpoint was the complete clinical response (cCR) rate. Secondary endpoints included bladder intact disease-free survival (BI-DFS), pathological downstaging (pDS) rate, and safety. Furthermore, we investigated the correlation between cCR and HER2 expression levels. Results: This study enrolled 47 patients between June27, 2022, and October 20, 2023. The median age was 66.0 years, with male representation at 85.1%. Baseline molecular profiling revealed varying levels of HER2 expression: HER2 IHC 3+ (17.0%), HER2 IHC 2+ (48.9%), and HER2 IHC 1+ (34.0%). The median number of treatment cycles administered was 4 ( 3.0-9.0). Remarkably, out of 47 patients, 29 achieved cCR (61.7%). This cCR rate positively correlated with the levels of HER2 expression. Additionally, 37 of the 47 patients achieved pDS (78.7%). Post neoadjuvant therapy, 30 patients opted for bladder-preserving and the rest underwent RC. Over a median follow-up period of 8.0 months (3.0-14.0), the median BI-DFS was not reached, with a 1-year BI-DFS rate of 100%. The most common TRAEs of any grade included anorexia (68.1%), peripheral sensory neuropathy (66.0%), and fatigue (61.7%). Grade 3 or worse TRAEs occurred in 25% of patients, primarily involving anemia, elevated ALT, and fatigue. Conclusions: The combination of DV and Toripalimab as neoadjuvant therapy demonstrated notable efficacy and a manageable safety profile in patients with HER2-expressing MIBC followed by either selective bladder preservation or RC.