Updated Results of PURE-01 with Preliminary Activity of Neoadjuvant Pembrolizumab in Patients with Muscle-invasive Bladder Carcinoma with Variant Histologies
Updated Results of PURE-01 with Preliminary Activity of Neoadjuvant Pembrolizumab in Patients with Muscle-invasive Bladder Carcinoma with Variant Histologies
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DOI：
10.1016/j.eururo.2019.10.026
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发表时间：
2020-04-01
期刊：
影响因子：
23.4
通讯作者：
Montorsi, Francesco
中科院分区：
文献类型：
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作者：
Necchi, Andrea;Raggi, Daniele;Montorsi, Francesco
背景：膀胱肿瘤的主要变异组织学(VH)患者，定义为肿瘤标本的50%受累，通常被排除在临床试验之外，对于这些患者，标准化疗的疗效是有限的。目的：评价Pembrolizumab在肌肉浸润性膀胱癌(MIBC)和VH患者中的活性，纳入Pure-01研究(NCT02736266)。设计、背景和对象：在开放标记的单臂Pure-01研究中，T2-4aN0M0 M0 MIBC患者在根治性膀胱切除术(RC)前接受三个疗程200 mg的Pembrolizumab治疗。修改后的研究设计包括以VH为主的患者。干预：新辅助剂Pembrolizumab和RC。结果测量和统计分析：意向治疗人群中的病理完全应答(PT0)是主要终点。生物标志物分析包括使用联合阳性评分(CPS；DAKO 22C3抗体)和综合基因组图谱(FoundationOne分析)的程序性细胞死亡配体-1(PD-L1)表达。多变量Logistic回归分析(MVA)评估了组织学类型(主要的VH与非主要的VH与纯尿路上皮癌)、肿瘤突变负荷(TMB)和CPS与病理反应的关系。结果与限制：从2017年2月至2019年6月，114例患者入选；其中34例(30%)出现VH，其中19例(17%)以VH为主。总的PTO发生率为37%(95%可信区间：28-46)，PT
Background: Patients with predominant variant histology (VH) of bladder tumors, defined as involving >50 % of the tumor specimens, are typically excluded from clinical trials, and for these patients, the efficacy of standard chemotherapy is limited.Objective: To evaluate the activity of preoperative pembrolizumab in patients with muscleinvasive bladder carcinoma (MIBC) and VH, enrolled in PURE-01 study (NCT02736266).Design, setting, and participants: In the open-label, single-arm, phase 2 PURE-01 study, three courses of 200 mg pembrolizumab preceding radical cystectomy (RC) were administered in T2-4aN0M0 MIBC patients. The amended study design included patients with predominant VH.Intervention: Neoadjuvant pembrolizumab and RC.Outcome measurements and statistical analysis: Pathological complete response (pT0) in intention-to-treat population was the primary endpoint. Biomarker analyses included programmed cell-death ligand-1 (PD-L1) expression using the combined positive score (CPS; Dako 22C3 antibody) and comprehensive genomic profiling (FoundationOne assay). Multivariable logistic regression analyses (MVAs) evaluated the histological category (predominant VH vs nonpredominant VH vs pure urothelial carcinoma), tumor mutational burden (TMB) and CPS in association with the pathological response.Results and limitations: From February 2017 to June 2019, 114 patients were enrolled; 34 (30%) of them presented with VH, including 19 (17%) with predominant VH. In total, the pTO rate was 37% (95% confidence interval [CI]: 28-46) and the pT