Efficacy and safety of disitamab vedotin in combination with immune checkpoint inhibitors in patients with locally advanced or metastatic urothelial carcinoma.

Introduction: Disitamab Vedotin (DV, RC48, or RC48-ADC) is a novel humanized antibody-drug conjugate (ADC), which is based on human epidermal growth factor receptor 2 antibody (anti-HER2, or hertuzumab) coupled with monomethyl auristatin E (MMAE). This study aims to evaluate the efficacy and safety of RC48-ADC in combination with programmed cell death protein 1 (PD-1) inhibitors for treatment of locally advanced or metastatic urothelial carcinoma (la/mUC) patients.

Patients and methods: This is a retrospective and real-world investigation originated from an enrollment of locally advanced or mUC patients underwent treatments with RC48-ADC in combination with PD-1 inhibitors in two hospitals, between August 2022 and July 2024. The overall objective response rate (ORR), disease control rate (DCR), median overall survival (mOS), median Progression Free Survival (mPFS) and safety were assessed.

Results: Totally 51 locally advanced or mUC patients were included in this study, with the following background: age range (39-86 years old), gender (39 (76.5%) male, 12 (23.5%) female). Treatment outcomes included complete remission (27.5%), partial remission (33.3%), stable disease (13.7%), and disease progression (25.5%), yielding an ORR of 61% (95% CI:47-73%) and DCR of 75% (95% CI:61-84%). Until July 2024, the median overall survival (mOS) for all patients was not reached, the median progression-free survival (mPFS) for all patients was 9 months (95% CI:5.8-12.1).Treatment-related adverse events occurred in all patients and the most common side effects were anorexia, asthenia, rash, and pruritus. These adverse symptoms were readily manageable and could be relieved by symptomatic treatment.

Conclusion: RC48-ADC in combination with PD-1 immunotherapy has promising efficacy and manageable safety for locally advanced or mUC patients in real-world settings.