Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Genitourinary Oncology, Peking University Cancer Hospital and Institute, Beijing, China.
Department of Urology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China.
Clin Cancer Res. 2022 Feb 1;28(3):489-497. doi: 10.1158/1078-0432.CCR-21-2210. Epub 2021 Nov 5.
Immunotherapy offers a second-line option for patients with metastatic urothelial carcinoma (mUC) who failed standard therapy, but the biomarkers for predicting response remain to be explored. This study aims to evaluate the safety, efficacy, and correlative biomarker of toripalimab in patients with previously treated mUC.
Patients with mUC received toripalimab 3 mg/kg Q2W. Clinical response was assessed every 8 weeks by an independent review committee per RECIST v1.1. Tumor PD-L1 expression, tumor mutational burden (TMB), and other biomarkers were evaluated.
Among the intention-to-treat population ( = 151), 85% of the patients experienced treatment-related adverse event (TRAE) and 20% experienced grade 3 and above TRAE. The objective response rate (ORR) was 26% with a disease control rate (DCR) of 45%. The median duration of response, progression-free survival (PFS), and overall survival (OS) were 19.7 months [95% confidence interval (CI): 13.9-not estimable], 2.3 months (95% CI, 1.8-3.6), and 14.4 months (95% CI, 9.3-23.1), respectively. Both PD-L1 and TMB-high (10 mutations/Mb as the cutoff) patients had better ORR than PD-L1 patients (42% vs. 17%, = 0.002) and TMB-low patients (48% vs. 22%, = 0.014), respectively. The TMB-high group also showed better PFS (12.9 vs. 1.8 months, < 0.001) and OS (not reached versus 10.0 months, = 0.018) than the TMB-low group.
Toripalimab has demonstrated encouraging clinical activity in the second-line treatment of mUC with a manageable safety profile. PD-L1 expression and TMB were two independent biomarkers in the study.
免疫疗法为标准治疗失败的转移性尿路上皮癌（mUC）患者提供了二线选择，但预测反应的生物标志物仍有待探索。本研究旨在评估先前治疗过的 mUC 患者接受 toripalimab 的安全性、疗效和相关生物标志物。
mUC 患者接受 toripalimab 3 mg/kg Q2W 治疗。每 8 周通过独立审查委员会根据 RECIST v1.1 评估临床反应。评估肿瘤 PD-L1 表达、肿瘤突变负担（TMB）和其他生物标志物。
在意向治疗人群（n=151）中，85%的患者发生治疗相关不良事件（TRAE），20%的患者发生 3 级及以上 TRAE。客观缓解率（ORR）为 26%，疾病控制率（DCR）为 45%。中位缓解持续时间、无进展生存期（PFS）和总生存期（OS）分别为 19.7 个月[95%置信区间（CI）：13.9-不可估计]、2.3 个月（95%CI，1.8-3.6）和 14.4 个月（95%CI，9.3-23.1）。PD-L1 高（以 10 个突变/Mb 为截断值）和 TMB 高（10 个突变/Mb 为截断值）患者的 ORR 均优于 PD-L1 患者（42% vs. 17%， = 0.002）和 TMB 低患者（48% vs. 22%， = 0.014）。TMB 高组的 PFS（12.9 与 1.8 个月， < 0.001）和 OS（未达到与 10.0 个月， = 0.018）也优于 TMB 低组。
toripalimab 在二线治疗 mUC 中显示出令人鼓舞的临床活性，具有可管理的安全性。PD-L1 表达和 TMB 是研究中的两个独立生物标志物。
