Real-world effectiveness of disitamab vedotin plus PD-1 inhibitor versus platinum-based chemotherapy as postoperative adjuvant therapy in high-risk upper tract urothelial carcinoma: A comparative study.

Abstract

4611 Background: Currently, gemcitabine–platinum combination chemotherapy represents the standard adjuvant regimen following radical surgery for high-risk upper tract urothelial carcinoma (UTUC), as it reduces the risk of disease progression in approximately half of all patients. Nevertheless, a substantial proportion of patients are ineligible for this standard regimen due to post-surgical complications like renal insufficiency. Disitamab vedotin (DV), an antibody–drug conjugate targeting HER-2, has recently been shown to yield superior outcomes in advanced urothelial carcinoma when combined with PD-1 inhibitor immunotherapy. Therefore, based on real-world data, this study aims to evaluate the efficacy of the DV plus PD-1 inhibitor versus standard gemcitabine–platinum chemotherapy in the operative adjuvant treatment of UTUC. Methods: A retrospective cohort analysis was conducted using data from UTUC patients at Peking University Cancer Hospital between January 2015 and June 2025. The study included UTUC patients diagnosed as pT 2–4a N 0 M 0 , who received either 4–6 cycles of DV combined with PD-1 inhibitors or gemcitabine–platinum (cisplatin or carboplatin selected based on postoperative renal function) combination chemotherapy. The primary endpoint was disease-free survival (DFS), the key secondary endpoint was treatment-related adverse events (TRAEs). Results: A total of 105 UTUC patients were enrolled, with a median follow-up of 45.7 months. Of these, 34 patients were treated with DV combined with PD-1 inhibitors (DV group), and 71 patients received chemotherapy. Compared with chemotherapy, the DV plus PD-1 inhibitor significantly prolonged DFS, with a hazard ratio of 0.29 (95% CI 0.09–0.98; P = 0.047). The estimated 3-year DFS rates were 83.1% (95% CI 66.8–100.0) in the DV group and 64.9% (95% CI 54.3–77.7) in the chemotherapy group. Regarding safety, grade ≥ 3 TRAEs occurred more frequently in the chemotherapy group than in the DV group (36.6% vs. 12.9%), mainly comprising hematologic toxicities. Conclusions: Disitamab vedotin combined with PD-1 inhibitor immunotherapy might improve DFS compared with standard chemotherapy as adjuvant therapy for UTUC. Supported by favorable efficacy and safety outcomes, this combination represents a promising postoperative treatment option. Participants’ and tumour characteristics. Total (n=105) DV group (n=34) Chemotherapy group (n=71) P value Age(years)，median(IQR) 63 (56.5-63) 65 (57-69) 63 (56-70) 0.848 Sex, n (%) Male 56 (53.3) 16 (47.1) 40 (56.3) 0.372 Female 49 (46.7) 18 (52.9) 31 (43.7) Pathological T stage pT2 37 (35.2) 11 (32.4) 26 (36.6) 0.453 pT3 58 (55.2) 18 (52.9) 40 (56.3) pT4 10 (9.5) 5 (14.7) 5 (7.0) Nodal stage N0 95 (90.5) 33 (97.1) 62 (87.3) 0.225 N1 5 (4.8) 0 (0) 5 (7.0) N2 5 (4.8) 1 (2.9) 4 (5.6)