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.
case_series · Level IV
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- Also identified by DOI 10.1097/JU.0000000000004993.
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Abstract
To evaluate the efficacy and safety of Toripalimab combined with gemcitabine and cisplatin (GC) as the neoadjuvant treatment (NAT) before radical cystectomy (RC) in patients with muscle-invasive bladder cancer (MIBC). This phase II trial enrolled 30 patients with T2-3N0M0 MIBC scheduled for RC. Patients received a treatment regimen of toripalimab 240 mg, gemcitabine 1000 mg/m<sup>2</sup>, and cisplatin 70 mg/m<sup>2</sup> on day 1, followed by gemcitabine 1000 mg/m<sup>2</sup> 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 (OS), and progression-free survival (PFS). The FISHER test was performed to analyze the relationship between genomic changes, tumor mutation burden (TMB), and pCR rate. 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 PFS rates were 85.2% and 77.6%, respectively; the 1-year and 3-year OS 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). Toripalimab combined with GC chemotherapy demonstrates a good efficacy and safety, making it a promising therapeutic strategy for NAT of MIBC. The clinical trial number for this study is ChiCTR2100051298.