Tislelizumab combined with gemcitabine and cisplatin (GC) as adjuvant therapy in patients with high-risk upper urothelial carcinoma (UTUC) after surgery: A 2-year follow-up, real-world study.

person Penghe Quan Department of Urology, Xijing Hospital, Air Force Military Medical University, Xi’an, China info_outline Penghe Quan, Haozhong Hou, Xiaojian Yang

Authors person Penghe Quan Department of Urology, Xijing Hospital, Air Force Military Medical University, Xi’an, China info_outline Penghe Quan, Haozhong Hou, Xiaojian Yang Organizations Department of Urology, Xijing Hospital, Air Force Military Medical University, Xi’an, China Abstract Disclosures Research Funding BeiGene, Inc. Background: In China, the prevalence of upper tract urothelial carcinoma (UTUC) among patients (pts) with urothelial carcinoma (UC) ranges from 9.3% to 19.9%, which is higher compared to the 5%-10% observed in Caucasoid populations. Following radical nephroureterectomy (RNU), UTUC pts with high-risk factors (e.g., local , pT3-4a, ypT2-4a, or N+) still have a poor prognosis and require adjuvant therapy. Immune checkpoint inhibitor as adjuvant therapy has been previously demonstrated improved disease-free survival (DFS) for UC pts, but the data from UTUC studies is limited.This real-world study aimed to evaluate the efficacy and safety of tislelizumab (Tisle) plus gemcitabine and cisplatin (GC) in high-risk UTUC pts. Methods: Pts who were diagnosed with T1N1 or T2-T4aN0-1M0 UTUC, tolerated surgery, and had adequate renal function reserve after surgery and Eastern Cooperative Oncology Group performance status (ECOG PS) of 0-1 were retrospectively enrolled from the Department of Urology, Xijing Hospital of Air Force Military Medical University between January 2020 and March 2023. Within 90 days following the RNU surgery, pts received adjuvant therapy of 200 mg Tisle on day 1 every 3 weeks plus 0-6 cycle GC chemotherapy (1000 mg/m 2 gemcitabine on days 1 and 8; 70 mg/m 2 cisplatin on day 2). Tisle was continued until disease progression or intolerable toxicity. The primary endpoint was 3-year DFS rate. Secondary endpoints were 5-year DFS rate, overall survival (OS), cancer-specific survival (CSS), and safety. Results: A total of 53 pts were enrolled in this study for efficacy evaluation. As of the cut-off date , median follow-up time was 26 (5-46) months, and of the pts were followed up for >24 months. The 2-year DFS rate was 75.56% (95% confidence intervals [CI], 57.87%-86.63%), and the 2-year OS rate was 79.63% (95% CI, 61.50%-89.88%). Compared to GC < 3 cycles, GC ≥ 3 cycles significantly improved DFS (hazard ratio [HR], 0.125; 95% CI, 0.034-0.461; p =0.019) and OS (HR, 0.147; 95% CI, 0.037-0.589; p =0.037), indicating a long tail in survival with the addition of Tisle to GC. Conclusions: In this real-world setting, adjuvant therapy with Tisle plus GC demonstrated encouraging efficacy and well-tolerated safety among high-risk UTUC pts. The final results will reported in further studies.