Postoperative adjuvant treatment of HER2 overexpression in upper urinary tract urothelial carcinoma with the combination of disitamab vedotin and toripalimab: A real-world retrospective study.

Abstract

673 Background: Radical nephroureterectomy (RNU) bears a high recurrence risk. Thus, postoperative treatment is necessary for upper urinary tract urothelial carcinoma (UTUC) patients. The CheckMate-274 study proved the feasibility of immunotherapy after surgery for urothelial carcinoma (UC), but showing no significant efficacy difference compared to placebo in UTUC. Disitamab vedotin is an antibody-drug conjugate (ADC) composed of an anti-HER2 antibody disitamab and MMAE payload. Clinical studies have showed that combining Disitamab vedotin with Toripalimab is an efficacious regimen for advanced urothelial carcinoma. Thus, we are investigating whether this combination therapy following RNU can offer improved survival outcomes. Methods: A retrospective analysis was conducted on data from patients who underwent RNU at Nanjing Drum Tower Hospital between April 2022 and April 2024. The study included patients pathologically diagnosed with cT 2-4a N 0 M 0 UTUC and HER2 positive status (HER2 IHC2+ or HER2 IHC3+). Patients received 26 cycles of Toripalimab (240mg, IV, Day 1, q2w) combined with 8 cycles of Disitamab vedotin (2mg/kg, IV, Day 1,q2w). CT scans of the chest and abdomen were performed every three months. The primary endpoint was the 12-month disease-free survival (DFS) rate. Results: The study included 36 cases of UTUC patients after RNU. Among them, 12 cases received treatment with Disitamab vedotin combined with Toripalimab, while 24 cases did not receive postoperative adjuvant therapy. In the treatment group, the 12-month DFS rate was 91.7% (1/12), compared to 62.5% (9/24) in the non-adjuvant therapy group. The most common treatment-related adverse events (TRAEs) in the treatment group were abnormal liver function (41.6%), decreased appetite (50%), and peripheral sensory neuropathy (33.3%), with no Grade 3 or higher adverse events observed. Conclusions: Disitamab vedotin combined with Toripalimab demonstrated efficacy as adjuvant therapy following radical nephroureterectomy for UTUC. Based on the one-year DFS outcomes, this combination could be considered as an adjuvant therapy option post-surgery.