Neoadjuvant吉西他滨 - cisplatin和具有可切除肌肉侵入性膀胱癌的人的Tislelizumab：多中心，单臂2期试验
Neoadjuvant gemcitabine-cisplatin plus tislelizumab in persons with resectable muscle-invasive bladder cancer: a multicenter, single-arm, phase 2 trial
影响因子:28.50000
分区:医学1区 Top / 肿瘤学1区
发表日期:2024 Oct
作者:
Kaiwen Li, Wenlong Zhong, Jinhai Fan, Shaogang Wang, Dexin Yu, Tao Xu, Jiaju Lyu, Shaoxu Wu, Tao Qin, Zhuo Wu, Longhao Xu, Kaijie Wu, Zheng Liu, Zhiquan Hu, Fan Li, Jinyou Wang, Qi Wang, Jie Min, Zhiqiang Zhang, Luping Yu, Sentai Ding, Longfei Huang, Tingting Zhao, Jian Huang, Tianxin Lin
摘要
程序死亡1封锁（Tislelizumab）已被批准用于转移性尿路上皮癌，但不作为新辅助治疗肌肉侵入性膀胱癌（MIBC）的一部分。在这项多中心单臂试验（CHICTR2000037670）中，有65名CT2-4AN0M0 MIBC的参与者接受了Neoadjuvant Gemcitabine-Cisplatin和Tislelizumab；其中57例接受了自由基膀胱切除术（RC）。病理完全反应（PCR）率的主要终点为50.9％（29/57，95％置信区间（CI）37.3-64.4％），在接受参与者中，病理降低（次要端点）率为75.4％（43/57，43/57，95％CI 62.2-85.9％）在参与者中。基因组和转录组分析揭示了三个MIBC分子亚型（S）：S1（免疫 - 溶剂），具有活化的细胞周期途径，S2（免疫分离），具有活化转化的转化生长因子-β途径和S3（免疫功能）（免疫功能），并具有上调的干扰素-α和干扰素-α和干扰素-CENTRAM。事后分析显示，PCR率为16％（3/19，S1），77％（10/13，S2）和80％（12/15，S3）（p = 0.006）。总之，新辅助吉西他滨 - 清铂和用于MIBC的Tislelizumab与PCR率提高兼容。
Abstract
Programmed death 1 blockade (tislelizumab) has been approved for metastatic urothelial carcinoma but not as part of neoadjuvant therapy for muscle-invasive bladder cancer (MIBC). In this multicenter single-arm trial (ChiCTR2000037670), 65 participants with cT2-4aN0M0 MIBC received neoadjuvant gemcitabine-cisplatin plus tislelizumab; 57 of them underwent radical cystectomy (RC). The primary endpoint of pathologic complete response (pCR) rate was 50.9% (29/57, 95% confidence interval (CI) 37.3-64.4%) and the pathologic downstaging (secondary endpoint) rate was 75.4% (43/57, 95% CI 62.2-85.9%) in participants undergoing RC. Genomic and transcriptomic analyses revealed three MIBC molecular subtypes (S): S1 (immune-desert) with activated cell-cycle pathway, S2 (immune-excluded) with activated transforming growth factor-β pathway and S3 (immune-inflamed) with upregulated interferon-α and interferon-γ response. Post hoc analysis showed pCR rates of 16% (3/19, S1), 77% (10/13, S2) and 80% (12/15, S3) (P = 0.006). In conclusion, neoadjuvant gemcitabine-cisplatin plus tislelizumab for MIBC was compatible with an enhanced pCR rate.