Efficacy, Safety, and Biomarker Analysis of Toripalimab Monoclonal Antibody Combined With Gemcitabine and Cisplatin Chemotherapy as Neoadjuvant Treatment in Muscle-Invasive Bladder Cancer: A Phase II Clinical Trial

PURPOSE: We evaluated the efficacy and safety of toripalimab combined with gemcitabine and cisplatin as the neoadjuvant treatment (NAT) before radical cystectomy (RC) in patients with muscle-invasive bladder cancer (MIBC). MATERIALS AND METHODS: on day 8, in 21-day cycles for a total of 4 cycles. RC was scheduled 4 to 6 weeks after the last treatment cycle. The primary end point is the pathological complete response (pCR), and the secondary end points are safety, overall survival, and progression-free survival. The Fisher exact test test was performed to analyze the relationship between genomic changes, tumor mutation burden, and pCR rate. RESULTS: From January 2020 to December 2021, 27 patients underwent RC after NAT, and 3 withdrew from the study. The pCR rate reached 40.7% (11/27). The 1-year and 3-year progression-free survival rates were 85.2% and 77.6%, respectively; the 1-year and 3-year overall survival rates were 96.2% and 84.6%, respectively. Among the 18 patients who retained the target lesions during NAT, the pCR rate was 27.8% (5/18) and the pathological response rate was 50.0% (9/18). The rate of adverse events of grade 3 or higher was 13.3%. Biomarker analysis indicated that patients with dual-mutation in KMT2D, ERBB2, or EPHA2 genes had a lower pCR rate following NAT. In the patients with PD-L1 expression ≥ 5% (n = 16), the pCR and pathological response rate were 43.8% (7/16) and 68.8% (11/16), respectively. In patients with PD-L1 expression < 5% (n = 11), the pCR rate was 36.4% (4/11) and the pathological response rate was 63.6% (7/11). CONCLUSIONS: Toripalimab combined with gemcitabine and cisplatin chemotherapy demonstrates a good efficacy and safety, making it a promising therapeutic strategy for NAT of MIBC. TRIAL REGISTRATION: The clinical trial number for this study is ChiCTR2100051298.