Radical nephroureterectomy (RNU) is associated with a high risk of recurrence, highlighting the need for postoperative treatment in patients with upper urinary tract urothelial carcinoma (UTUC). The CheckMate-274 study demonstrated the feasibility of immunotherapy after surgery for urothelial carcinoma (UC), but no significant efficacy was observed for UTUC compared to placebo. Disitamab vedotin, an antibody-drug conjugate (ADC) composed of an anti-HER2 antibody (disitamab) linked to an MMAE payload, has shown efficacy in combination with Toripalimab in clinical studies for advanced urothelial carcinoma. This study aims to evaluate whether this combination therapy following RNU can improve survival outcomes in UTUC.

We conducted a retrospective analysis of patients who underwent RNU at Nanjing Drum Tower Hospital from April 2022 to April 2024. The study included patients with pathologically confirmed cT2-4aN0M0 UTUC and HER2-positive status (HER2 IHC2+ or HER2 IHC3+). Patients received 26 cycles of Toripalimab (240 mg, IV, Day 1, q2w) combined with 8 cycles of Disitamab vedotin (2 mg/kg, IV, Day 1, q2w). Chest and abdominal CT scans were performed every three months. The primary endpoint was the 18-month disease-free survival (DFS) rate.

A total of 36 UTUC patients post-RNU were included in the study. Of these, 12 received adjuvant therapy with Disitamab vedotin and Toripalimab, while 24 did not receive postoperative adjuvant treatment. The 18-month DFS rate was 83.3% (10/12) in the treatment group, compared to 41.7% (10/24) in the non-adjuvant therapy group. The most common treatment-related adverse events (TRAEs) in the treatment group were abnormal liver function (50.0%), decreased appetite (50%), and peripheral sensory neuropathy (33.3%), with no Grade 3 or higher adverse events reported.

Disitamab vedotin combined with Toripalimab showed promising efficacy as adjuvant therapy following RNU for UTUC. Based on the one-year DFS outcomes, this combination may be considered as a potential adjuvant therapy option post-surgery.