(UroToday.com) The American Urological Association's 2025 Annual Meeting, in Las Vegas, Nevada, was host to the IP24: Bladder Cancer: Invasive II Session. Dr Yongbao Wei presented a Retrospective Multicenter Study evaluating Neoadjuvant Therapy with Combined Targeted HER2 and Immunotherapy for T2-T4N0-1M0 Bladder Cancer.
Dr. Wei began his presentation by emphasizing that neoadjuvant therapy is a key component in the management of locally advanced bladder cancer (T2–T4N0–1M0), as it has been shown to improve survival outcomes in multiple clinical studies.1,2
The investigators evaluated the efficacy and safety of combining HER2-targeted therapy with immunotherapy as a neoadjuvant treatment strategy for patients with locally advanced bladder cancer. HER2-targeted therapy involves inhibiting the human epidermal growth factor receptor 2 (HER2), a protein that promotes cell growth and is overexpressed in a subset of urothelial carcinomas. By blocking HER2 signaling using monoclonal antibodies, antibody-drug conjugates, or tyrosine kinase inhibitors, these therapies aim to suppress tumor progression and enhance the effectiveness of immunotherapy.
This retrospective, single-arm, multicenter study included 53 patients with T2–T4N0–1M0 bladder cancer who received neoadjuvant therapy combining RC48 (disitamab vedotin) with either toripalimab or tislelizumab between January 2019 and June 2024. RC48, an anti-HER2 antibody-drug conjugate, was administered at a dose of 2 mg/kg every two weeks. Immunotherapy was given as either toripalimab (3 mg/kg every three weeks) or tislelizumab (200 mg every three weeks), depending on the selected treatment regimen.
The primary endpoints were pathological complete response (pCR) and major pathological response (MPR). Secondary endpoints included progression-free survival (PFS), overall survival (OS), and safety.
Dr. Wei reported that combination therapy with RC48 (disitamab vedotin) and either toripalimab or tislelizumab achieved a pathological complete response (pCR) rate of 32% and a major pathological response (MPR) rate of 58%.
At a median follow-up of 14 months, the progression-free survival (PFS) rate was 76%, and the overall survival (OS) rate was 83%.
The most common adverse events included fatigue (51%), gastrointestinal disturbances (40%), and mild infusion-related reactions (30%). Most adverse events were manageable, and no patients discontinued treatment due to severe toxicity.
Dr. Wei wrapped up the interactive poster with the following conclusions:
- The combination of RC48 (disitamab vedotin) with toripalimab or tislelizumab as neoadjuvant therapy for patients with T2–T4N0–1M0 bladder cancer demonstrated encouraging outcomes in terms of pathological response, progression-free survival, and overall survival.
- The regimen was well tolerated, with manageable adverse events and no treatment-related discontinuations.
- These findings support further investigation of this combination as a neoadjuvant treatment strategy, particularly for patients with locally advanced disease.
- Long-term follow-up and larger, prospective studies are warranted to confirm these results.
Presented by: Yongbao Wei, MD, Associate Professor and Senior Researcher at Fujian Provincial Hospital. Fuzhou, China.
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 American Urological Association (AUA) annual meeting held in Las Vegas, NV, Saturday, April 26 - Tuesday, April 29, 2025
References
- Grossman HB, Natale RB, Tangen CM, et al. Neoadjuvant chemotherapy plus cystectomy compared with cystectomy alone for locally advanced bladder cancer. N Engl J Med. 2003;349(9):859–866. doi:10.1056/NEJMoa022148
- Advanced Bladder Cancer Meta-analysis Collaboration. Neoadjuvant chemotherapy in invasive bladder cancer: a systematic review and meta-analysis. Lancet. 2003;361(9373):1927–1934. doi:10.1016/S0140-6736(03)13580-7