Abstract
BACKGROUND: Urothelial carcinoma (UC) is an aggressive malignancy with limited options for patients unresponsive to chemotherapy or immunotherapy. Disitamab vedotin (RC48), a HER2-targeted antibody-drug conjugate(ADC), has shown promising results in clinical trials, but real-world data are lacking. METHODS: We conducted a single-center retrospective study of patients with histologically confirmed UC who received RC48 alone or in combination with PD-1 inhibitors between August 2022 and June 2024. Key inclusion criteria were at least one measurable lesion and adequate organ function; patients with incomplete records, concurrent active malignancies, or severe organ dysfunction precluding systemic therapy were excluded. RESULTS: A total of 71 patients were included. The ORR was 69.0%, including 15 complete and 34 partial responses. The median PFS was 24 months, and OS data were immature at cutoff. In subgroup analyses, patients receiving RC48 + PD-1 inhibitors achieved an ORR of 70.0% versus 63.6% with RC48 monotherapy. Grade ≥ 3 treatment-related adverse events occurred in 21.1% of patients, most commonly anemia and decreased appetite; events were generally manageable with supportive care and dose modification. CONCLUSIONS: RC48 showed encouraging activity and manageable safety in a real-world UC cohort. Prospective multicenter studies with longer follow-up are needed to validate these findings, compare monotherapy versus combination strategies, and define the optimal role of RC48 across UC disease stages.