Long-term efficacy and safety of disitamab vedotin monotherapy versus chemotherapy in bladder-preserving treatment of Chinese real-world patients with muscle-invasive urothelial cancer: A retrospective real-world study.

Abstract

e16578 Background: The validity and effectiveness of Trimodality Therapy (TMT) which employing optimizing transurethral resection of bladder tumors (TURBT), radiotherapy and integrating systemic chemotherapy have been supported by some empirical research studies. Novel antibody-drug conjugates (ADCs) such as Disitamab Vedotin (DV, RC48-ADC) have demonstrated significant better efficacy and safety than chemotherapy in urothelial carcinoma. This study was conducted to evaluate the clinical outcomes of RC48-ADC monotherapy compared with chemotherapy in the context of bladder-sparing TMT of real-world patients with muscle-invasive urothelial cancer (MIUC). Methods: This investigation retrospectively analyses data of 217 patients with muscle-invasive bladder cancer (MIBC), including 13 primary upper tract urothelial carcinoma (UTUC), who underwent bladder-preserving treatment at Tianjin Union Medical Center, Nankai University between January 2019 and May 2021. All patients were ineligible or refused radical cystectomy (RC) and received TURBT and synchrotron radiation (50-70 Gy) and/or nephroureterectomy (for UTUC). 175 followed by Gemcitabine plus Cisplatin including 92 HER2-negative (IHC 0/1+, GC-N-group) and 83 HER2-positive (IHC 2+ or 3+, GC-P-group), other 42 HER2-positive received RC48-ADC monotherapy (ADC-group). Last follow-up on 31 December 2023 (median follow-up: 38.1 months). Results: By the last follow-up date, 123 patients (53.0%) relapsed and 39 (18.0%) undergo salvage cystectomy of the enrolled 217 patients (173 males; median age 78 y [40-96]). 125 patients (57.6%) were HER2-positive, including 42 and 83 grouped in ADC-group and GC-P-group respectively, with larger, multiple, late stage, lymph nodes positive, glandular or sarcomatoid histology tumor and poor prognosis. The ADC-group demonstrate significant better long-term efficacy and safety compared to GC-P-group, the relapse rate was 35.7% vs. 67.5% (P < 0.005), mRFS was not reached (NE) vs. 19.0-mo (P < 0.005) and mOS was NE vs. 56.0-mo, with 66.7% vs. 92.8% experienced treatment-related adverse events (TRAEs) and 28.6% vs. 53.0% ≥ grade 3 TRAEs. The most common TRAEs were ALT/AST increased (45.2%), pruritus (38.1%), fatigue (33.3%) in ADC-group and appetite loss (80.7%), nausea (53.0%), anemia (49.4%) in GC-P-group. Conclusions: This retrospective study reaffirms that HER2-positivity was a significantly independent prognostic factor in MIUC. And RC48-ADC monotherapy proves to be a viable and safe option with long-term clinical outcomes for HER2-positive MIUC bladder-preserving treatment in the context of TMT, particularly for patients who are ineligible for surgery and chemotherapy. This approach offers a promising new direction for bladder-sparing therapy in MIUC.