Real-world efficacy and safety of disitamab vedotin (RC48) plus PD-1 inhibitors in advanced urothelial carcinoma: a single-center retrospective study.

[BACKGROUND] Urothelial carcinoma (UC) is a common malignancy with poor prognosis in refractory or metastatic stages. While platinum-based chemotherapy and PD-1 inhibitors have improved outcomes for some, the benefits are limited. Disitamab Vedotin (RC48), an HER2-targeted antibody-drug conjugate, combined with PD-1 inhibitors, has shown promising antitumor activity in advanced UC. This study aims to evaluate the clinical efficacy and safety of RC48 combined with PD-1 inhibitors in previously treated UC patients using real-world data.

[METHODS] This single-center, retrospective real-world study included 29 patients with mUC who had received prior treatment and were treated with RC48 plus a PD-1 inhibitor between October 2021 and April 2025. Treatment efficacy was assessed according to the Response Evaluation Criteria in Solid Tumours (RECIST 1.1). Primary endpoints were progression-free survival (PFS) and overall survival (OS). Secondary endpoints included objective response rate (ORR) and disease control rate (DCR). Treatment-related adverse events (TRAEs) were recorded and graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Subgroup analyses were conducted based on age, Eastern Cooperative Oncology Group (ECOG) performance status, tumor human epidermal growth factor receptor 2 (HER2) immunohistochemistry (IHC) status, number of metastatic sites, and programmed cell death ligand 1 (PD-L1) expression.

[RESULTS] Among 29 included patients, the median age was 67 years, and 69.0% were male. HER2 IHC showed 2+ expression in 51.7% of patients and 3+ expression in 20.7%. The vast majority of patients (93.1%) received ≥4 treatment cycles. The ORR was 34.5%, with a DCR of 96.6%. Disease progression occurred in only 1 patient (3.4%). Median PFS was 14.22 months. In an exploratory preliminary analysis with limited sample size, patients aged ≥65 years, ECOG performance status 0, and HER2 IHC 3+ numerically demonstrated longer PFS. The OS endpoint had not been reached at data cutoff; preliminary survival differences were observed in patients with ≤2 metastatic sites. Regarding safety, TRAEs occurred in 82.8% of patients, primarily peripheral neuropathy (48.28%), anemia (17.24%), and leukopenia (10.34%). Grade ≥3 TRAEs were reported in 6.9% of patients, with no treatment-related deaths recorded. Most adverse events were manageable through dose adjustments or supportive care.

[CONCLUSIONS] This retrospective real-world study provides preliminary evidence that RC48 combined with PD-1 inhibitors may offer encouraging antitumor activity and a manageable safety profile in relapsed or refractory mUC, with a median PFS of 14.22 months and a high DCR observed in this cohort. Given the exploratory nature of this analysis and the study's limitations, including the small sample size, single-center design, and lack of a control arm, these findings should be interpreted with caution. Larger prospective studies are warranted to validate these results.