Neoadjuvant cisplatin-based combination chemotherapy, typically combined with gemcitabine, is the standard first-line treatment for muscle-invasive bladder cancer (MIBC) and has been shown to improve overall survival (OS) by approximately 8% at five years. However, due to the high toxicity of cisplatin, patients with impaired renal function or those unable to tolerate cisplatin may be ineligible for this treatment. Disitamab Vedotin (DV), a humanized anti-HER2 monoclonal antibody conjugated with monomethyl auristatin E, has demonstrated promising efficacy and safety in the treatment of metastatic or advanced urothelial carcinoma. This study aims to evaluate the efficacy and safety of neoadjuvant treatment with DV in combination with immune checkpoint inhibitors for cisplatin-intolerant patients with MIBC.

This retrospective, single-center study included 26 patients with pathologically confirmed muscle-invasive urothelial carcinoma (T2-4N0-1M0) who were ineligible for cisplatin treatment due to renal dysfunction or could not tolerate cisplatin-based first-line chemotherapy due to adverse effects. The treatment regimen consisted of Disitamab Vedotin (DV) at 2 mg/kg every two weeks via intravenous injection, combined with Pembrolizumab or Tislelizumab at 200 mg, or Toripalimab at 3.0 mg/kg every three weeks via intravenous injection. The primary endpoint was pathological complete response (pCR), while secondary endpoints included the pathological downstage rate and safety profile. Additionally, factors associated with pCR were further explored through additional analysis.

A total of 26 patients（65.65± 8.40 years old）were included in this study, with 18 (69.2%) being male. Prior to neoadjuvant therapy, HER-2 IHC staining revealed that 1 patient (3.8%) had a HER-2 score of 1+, 13 patients (50%) had a score of 2+, and 12 patients (46.2%) had a score of 3+. The median number of treatment cycles for Disitamab Vedotin (DV) was 5 (range, 4–6). Notably, 10 patients (38.5%) achieved a pathological complete response (pCR), and 19 patients (73.1%) experienced pathological downstaging. The most common adverse events were rash (38.5%), nausea (26.9%), fatigue (23.1%), and hypothyroidism (7.7%). No grade 3-4 adverse events were observed. Furthermore, univariate and multivariate Cox regression analyses revealed that pCR rates were significantly associated with high HER-2 expression. Interestingly, 1 patient with a HER-2 score of 1+ still achieved pCR after treatment.

Neoadjuvant treatment with Disitamab Vedotin (DV) in combination with immune checkpoint inhibitors demonstrated promising efficacy and safety in cisplatin-intolerant patients with muscle-invasive bladder cancer (MIBC).