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Clinicopathological and molecular correlates of clinical benefit from disitamab vedotin (RC48), a HER-2-targeting antibody-drug conjugate, in metastatic urothelial carcinoma: a multi-center, real-world study

Year: 2025

Type: article

Abstract: INTRODUCTION: Disitamab Vedotin (DV), a HER-2-targeting antibody-drug conjugate, has exhibited substantial clinical advantages in individuals with metastatic urothelial carcinoma (mUC). Nonetheless, the extent of therapeutic efficacy in real-world scenarios for mUC patients and the specific patient profiles with the most benefit from DV remain unclear. METHODS: In this multi-center, retrospective, observational study, a total of 30 patients with mUC were included between April 2021 and March 2024 from three distinct hospitals, along with clinicopathological features and targeted sequencing data. Our analysis encompassed the assessment of the objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and the incidence of treatment-related adverse events (TrAEs). RESULTS: In the general population, the median follow-up time was 12.1 months, and the median OS was not reached with a 12-month OS rate of 86.7%. The median PFS was 12.2 months (95% confidence interval [CI]: 6.6-17.7 months), with an ORR of 42.3% (95% CI: 23.4%-63.1%) and a DCR of 73.1% (95% CI: 55.2%-88.4%). Higher HER-2 expression is correlated with prolonged clinical benefit from DV (Log-rank P = 0.082. HER-2 IHC 2+ & 3 + vs. IHC 1+: Median PFS: 13.1 vs. 4.6 months; Response rate: 60.0% vs. 0.0%). History of durable response to platinum-based chemotherapy can also imply longer PFS and better response rate (Log-rank P = 0.086. Median PFS: 14.2 vs. 3.6 months. Response rate: 50.0% vs. 10.0%). Moreover, higher mutation burden (TMB) is closely related to better outcomes from DV therapy (Log-rank P = 0.011. Median PFS: 12.8 vs. 4.6 months. Response rate: 71.4% vs. 11.1%. Firth's penalized multivariable Cox regression: P = 0.015. Hazard Ratio: 0.165. 95% CI: 0.026-0.717). CONCLUSION: In conclusion, patients with higher HER-2 expression, positive responses to chemotherapy, or elevated TMB are more likely to benefit from DV. These discoveries support the rationale for employing HER-2 antibody-drug conjugates (ADCs) for mUC patients.

Source: BMC Cancer

DOI: 10.1186/s12885-025-14870-x