(UroToday.com) The 2025 American Society of Clinical Oncology Genitourinary (ASCO GU) cancers symposium held in San Francisco, CA between February 13th and 15th 2025, was host to the Poster Session B: Urothelial Carcinoma. Dr. Shun Zhang presented Abstract 673: 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.
Radical nephroureterectomy remains the cornerstone of upper urinary tract urothelial carcinoma (UTUC) management, but it is associated with a high risk of recurrence, often necessitating adjuvant treatment. The CheckMate-274 study demonstrated improved survival outcomes for urothelial carcinoma (UC); however, it did not show a significant efficacy difference compared to placebo in patients with UTUC in the subgroup analysis, highlighting the need for more effective adjuvant strategies in this population.1
Disitamab vedotin is an antibody-drug conjugate (ADC) consisting of an anti-HER2 antibody, disitamab, linked to an MMAE payload. Clinical studies have shown that combining disitamab vedotin with toripalimab is an effective regimen for advanced urothelial carcinoma. Investigators are now evaluating whether this combination, when administered after radical nephroureterectomy, can improve survival outcomes in patients with HER2-overexpressing UTUC, potentially offering a novel adjuvant treatment strategy.
This retrospective analysis examined data from patients who underwent radical nephroureterectomy at Nanjing Drum Tower Hospital (China) between April 2022 and April 2024. The study included patients with pathologically confirmed cT2-4aN0M0 UTUC and HER2-positive status (HER2 IHC2+ or HER2 IHC3+).
Patients treated with the combination regimen received 26 cycles of toripalimab (240 mg IV, Day 1, q2w) alongside 8 cycles of disitamab vedotin (2 mg/kg IV, Day 1, q2w). Follow-up assessments included CT scans of the chest and abdomen every three months. The primary endpoint was the 12-month disease-free survival (DFS) rate.
The study included 36 patients with UTUC who underwent radical nephroureterectomy. Among them, 12 received adjuvant treatment with disitamab vedotin combined with toripalimab, while 24 did not receive postoperative adjuvant therapy. Notably, the majority of patients in the treatment group had HER2 2+ status (75%), while 25% had HER2 3+ status. Additionally, most patients in the treatment group (67%) had T3 disease, highlighting a population at higher risk for recurrence.
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%)
- Peripheral sensory neuropathy (33.3%)
No Grade 3 or higher adverse events were observed.
The investigators reached the following conclusions:
- Disitamab vedotin combined with Toripalimab demonstrated efficacy as adjuvant therapy following radical nephroureterectomy for UTUC.
- Disitamab Vedotin plus Toripalimab may enhance one-year postoperative DFS in UTUC patients with HER2-overexpression.
- Based on the one-year DFS outcomes, this combination could be considered as an adjuvant therapy option post-surgery.
Presented by: Shun Zhang, MD, Department of Urology at the Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing University of Chinese Medicine.
Written by: Julian Chavarriaga, MD – Urologic Oncologist at Cancer Treatment and Research Center (CTIC) via Society of Urologic Oncology (SUO) Fellow at The University of Toronto. @chavarriagaj on Twitter during the 2025 Genitourinary (GU) American Society of Clinical Oncology (ASCO) Annual Meeting, San Francisco, CA, Thurs, Feb 13 – Sat, Feb 15, 2025.
References:
- Bajorin DF, Witjes JA, Gschwend JE, Schenker M, Valderrama BP, Tomita Y, Bamias A, Lebret T, Shariat SF, Park SH, Ye D, Agerbaek M, Enting D, McDermott R, Gajate P, Peer A, Milowsky MI, Nosov A, Neif Antonio J Jr, Tupikowski K, Toms L, Fischer BS, Qureshi A, Collette S, Unsal-Kacmaz K, Broughton E, Zardavas D, Koon HB, Galsky MD. Adjuvant Nivolumab versus Placebo in Muscle-Invasive Urothelial Carcinoma. N Engl J Med. 2021 Jun 3;384(22):2102-2114. doi: 10.1056/NEJMoa2034442. Erratum in: N Engl J Med. 2021 Aug 26;385(9):864. doi: 10.1056/NEJMx210012. PMID: 34077643; PMCID: PMC8215888.