(UroToday.com) The 2025 AUA annual meeting featured an upper tract urothelial carcinoma session and a presentation by Dr. Shun Zhang discussing results of a retrospective study assessing postoperative adjuvant treatment of HER2-overexpressing upper tract urothelial carcinoma with disitamab vedotin and toripalimab. Radical nephroureterectomy is associated with a high risk of recurrence, highlighting the need for postoperative treatment in patients with upper tract urothelial carcinoma. The CheckMate-274 study demonstrated the feasibility of immunotherapy after surgery for urothelial carcinoma, but no significant efficacy was observed for upper tract urothelial carcinoma compared to placebo.1
Disitamab vedotin is an investigational antibody-drug conjugate comprising a fully humanized HER2-directed monoclonal antibody, disitamab, conjugated to MMAE via protease-cleavable mc-vc linker:
Toripalimab is an anti-tumor PD-1 antibody:
Disitamab vedotin in combination with toripalimab has shown efficacy in clinical studies for advanced urothelial carcinoma. This study, presented at AUA 2025, aimed to evaluate whether this combination therapy following radical nephroureterectomy can improve survival outcomes in upper tract urothelial carcinoma.
This was a retrospective analysis of patients who underwent radical nephroureterectomy at Nanjing Drum Tower Hospital from April 2022 to April 2024. The study included patients with pathologically confirmed cT2-4aN0M0 upper tract urothelial carcinoma 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 12-month disease-free survival rate.
A total of 36 upper tract urothelial carcinoma patients post-radical nephroureterectomy 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 12-month disease-free survival rate was 91.7% (11/12) in the treatment group, compared to 62.5% (15/24) in the non-adjuvant therapy group. The most common treatment related adverse events 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 reported.
Dr. Zhang concluded this presentation discussing results of a retrospective study assessing postoperative adjuvant treatment of HER2-overexpressing upper tract urothelial carcinoma with disitamab vedotin and toripalimab, with the following take home points:
- Disitamab vedotin combined with toripalimab showed promising efficacy as adjuvant therapy following radical nephroureterectomy for upper tract urothelial carcinoma
- Based on the one-year disease-free survival outcomes, this combination may be considered as a potential adjuvant therapy option post-surgery
Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Associate Professor of Urology, Georgia Cancer Center, Wellstar MCG Health, @zklaassen_md on Twitter during the 2025 American Urological Association (AUA) annual meeting held in Las Vegas, NV, Saturday, April 26 - Tuesday, April 29, 2025
References:
- Bajorin DF, Witjes JA, Gschwend JE, et al. Adjuvant nivolumab versus placebo in muscle-invasive urothelial carcinoma. N Engl J Med. 2021 Jun 3;384(22):2102-2114.