The efficacy and safety of antibody drug conjugate for high-risk non-muscle-invasive bladder cancer.
Authors: Li Hong Zheng , Hu Hailong , Niu Yuanjie , Guo Shizheng , Shen Chong , Jia Kaipeng , Huang Shiwang , Zhang Zhe , Qie Yunkai , An Zesheng , Wu Zhouliang , Bai Yiduo , Chen Houyuan 
Published: June 2023

e16616 Background: RC48 is a novel antibody drug conjugate that targets the Her2 protein and has shown promising efficacy in advanced urothelial cancer. However, its efficacy and safety in early-stage urothelial carcinoma are yet to be fully explored. To address this, we retrospectively collected the clinical data of patients with high-risk non-muscle-invasive bladder cancer (HR-NMIBC) who received rc48. Methods: In this retrospective study, 19 patients with Her2-overexpressing (IHC 2+ or 3+) HR-NMIBC who were unable to undergo complete tumor resection or tolerate surgery were included， and clinical data were retrospectively collected. Pathological complete response (CR), partial response (PR), stable disease (SD), objective response rate (ORR), duration of response (DOR), cystectomy-free survival (CFS), and event-free survival (EFS) were used for data analysis. Results: We collected clinical data from a total of 19 patients. The median age of patients was 69 years (range: 58 to 81). Seven patients (36.8%) received RC48 monotherapy, while 12 patients (63.2%) received RC48 combined with tislelizumab. A CR was achieved in 14 patients (73.7%, 95% CI: 48.6% to 89.9%), with a partial response (PR) in 1 patient (5.3%, 95% CI: 0.3% to 8.1%) and stable disease (SD) in 4 patients (21.1%, 95% CI: 7.0% to 46.1%). The overall ORR was 78.9% (95% CI: 53.9%, 93.0%). In 14 pts (73.7%) with Her2 IHC 3+, 12 achieved ORR, with an ORR of 85.7% (95% CI: 56.2%, 97.5%). Among the 5 pts with Her2 IHC 2+, 3 achieved ORR, with an ORR of 60.0% (95% CI: 17.0%, 92.7%). In addition, among the 5 pts who had prior PD-1 treatment failure, ORR was 60.0% (95% CI: 17.0%, 92.7%), and 2 achieved CR (40.0%, 95% CI: 7.3%, 83.0%). 1 patient died due to non-treatment-related causes. The duration of response (DOR) rate was 92.9% (95% CI: 80.3%, 100.0%), and the twelve-month DOR rate was 61.9% (95% CI: 27.4%, 100.0%). The twelve-month cystectomy-free survival (CFS) rate was 84.2% (95% CI: 69.3%, 100.0%), and the median CFS was not achieved. The twelve-month EFS rate was 75.8% (95% CI: 48.3%, 100.0%), and the median EFS was not achieved. The most commonly occurring grade 1-2 treatment-related adverse events (TRAEs) were alopecia (36.8%), rash (36.8%), pruritus (36.8%), anorexia (31.6%), and fatigue (26.3%). Grade 3-4 TRAEs were reported in 3 patients (6.3%), including rash, pruritus, leukopenia, and neutropenia. No grade 5 adverse events were reported. Conclusions: The results of this retrospective study show that both RC48 monotherapy and RC48 combined with tislelizumab have promising efficacy in the treatment of NMIBC. The overall response rate was high, with tolerable and manageable treatment-related adverse events. These findings suggest that RC48 monotherapy and RC48 combined with tislelizumab may be successful strategies for the treatment of NMIBC. Now, we are conducting a prospective study to further clarify the value of RC48 combining tislelizumab in NMIBC.