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RESEARCH ARTICLE

A real-world study of diverse RC48-based regimens across disease stages of urothelial carcinoma

Liangliang Qing1† ,  Lingyi Li2† ,  Qingchao Li3,4 ,  Yongjin Yang3,4 ,  Wenbo Xu3,4 ,  Yanan Wang3,4 ,  Rongxing Li3,4 ,  Chengyu You3,4 ,  Zhilong Dong3,4*
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1 Department of Urology, Zigong Fourth People’s Hospital, Zigong, Sichuan 643000, China
2 Department of Hospital Infection Management, Zigong Fourth People’s Hospital, Zigong, Sichuan 643000, China
3 Department of Urology, Lanzhou University Second Hospital, Lanzhou, Gansu 730030, China
4 Key Laboratory of Urological Disease of Gansu Province, Lanzhou University Second Hospital, Lanzhou, Gansu 730030, China
Bladder, e21200064 https://doi.org/10.14440/bladder.0169
Submitted: 10 June 2025 | Revised: 20 August 2025 | Accepted: 20 August 2025 | Published: 29 October 2025
© 2025 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
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Abstract

Background: RC48, a human epidermal growth factor receptor 2 (HER2)-targeting antibody–drug conjugate (ADC), has been approved in China for the treatment of HER2-positive metastatic urothelial carcinoma. Objective: This study evaluated the efficacy and safety of various RC48-based regimens in patients with urothelial carcinoma across disease stages in real-world settings. Methods: We retrospectively analyzed data from 56 patients at different disease stages who were treated at the Second Hospital of Lanzhou University between March 2023 and June 2024. RC48-ADC was administered as a monotherapy or in combination with immunotherapy until discontinuation due to disease progression, intolerable toxicity, death, or other reasons. Results: Outcomes included the objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and treatment-related adverse events (TRAEs). The median patient age was 67.5 years, with 83.9% being male. Of all patients, 14 (25.0%) received RC48-ADC monotherapy, and 42 (75.0%) received RC48-ADC combined with immunotherapy. Response rates were as follows: 15 patients (26.8%) achieved complete remission, 21 (37.5%) attained partial remission, 14 (25.0%) had stable disease, and 6 (10.7%) suffered from disease progression. The overall ORR was 64.3%, with rates of 70.0% and 60.0% in first-line and second-line treatment groups, respectively. The median PFS lasted for 6 months (range: 5–7 months), whereas the median OS was not reached. The most common TRAEs were peripheral sensory neuropathy (58.9%), fatigue (48.2%), decreased appetite (42.9%), and weight loss (37.5%). Conclusion: No increased incidence of TRAEs was observed in patients with poor performance status or impaired kidney function. RC48-ADC demonstrated efficacy and safety in patients with urothelial carcinoma, providing clinical benefits regardless of performance status or renal function.

Keywords
RC48
Antibody–drug conjugate
PD-1 inhibitor
Locally advanced or metastatic urothelial carcinoma
Efficacy and safety
Funding
This research was supported by the National Natural Science Foundation of China (Grant No. 82160148).
Conflict of interest
The authors declare that they have no competing interests.
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