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e16565 Background: The combination of antibody-drug conjugates and PD-1 inhibitor has great prospects for first-line treatment of advanced urothelial carcinoma (UC). This real-world study explored the efficacy, safety, and prognostic biomarkers of disitamab vedotin (DV) combined with PD-1 inhibitor, and compared them with other first-line regimens without DV. Methods: Patients were enrolled retrospectively from July 2021 to December 2022 in two cancer centers. There were four first-line treatment regimens: DV (120-180mg) plus PD-1 inhibitor (Tislelizumab 200mg or Toripalimab 240mg) once every 3 weeks, chemotherapy (gemcitabine plus cisplatin/carboplatin) plus ICI, chemotherapy, and ICI. Then patients were classified into the DV group and No DV group. Treatment outcomes were compared between the two groups after 1:1 ratio PS matching adjusted for sex, PS score, stage, histological grade, and tumor location. In DV group, RNA-seq was used to analyze differential expressed genes (DEGs). Results: There are 63 patients enrolled with median age 68 years (44–90 years). The median follow-up time was 13 months (4–36 months). The 1-year overall survival and progression free survival (PFS) rates were 74.3% and 47%, respectively. There were 30 patients received DV plus ICI, 17 received chemotherapy plus ICI, 9 received chemotherapy, and 7 received ICI alone. PS score and first-line regimen containing DV are independent prognostic factors for PFS. After PS matching, there were 22 patients each in the DV group and No DV group. There were significant differences between the two groups in terms of objective response rate (81.8% vs.27.3%, p=0.003) and 1-year PFS rate (68.2% vs.33.5%, p=0.008) (Table). In safety, hematology and gastrointestinal toxicity were more likely to occur in the No DV group, while neurotoxicity and rash were more likely to occur in the DV group, and most of which were grade 1-2. In DV group, the top 5 most significantly DEGs between patients with long (>6 months) and short PFS (≤6 months)were SCGB1A1, AKR1C1, FAM205C, ACP7 and NLGN4X, and which are enriched in the pathway of cytoplasmic translocation and the function of ribosome. Conclusions: The first-line regimen of DV plus PD-1 inhibitor for patients with advanced UC was more effective and safer than the regimen without DV. The pathway of cytoplasmic translocation and the function of ribosome may be highly correlated to the effectiveness of the regimen of ADC plus ICI. Table: see text
Jiang et al. (Sat,) studied this question.