Pembrolizumab as Neoadjuvant Therapy Before Radical Cystectomy in Patients With Muscle-Invasive Urothelial Bladder Carcinoma (PURE-01): An Open-Label, Single-Arm, Phase II Study
Pembrolizumab as Neoadjuvant Therapy Before Radical Cystectomy in Patients With Muscle-Invasive Urothelial Bladder Carcinoma (PURE-01): An Open-Label, Single-Arm, Phase II Study
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DOI：
10.1200/jco.18.01148
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发表时间：
2018-12-01
影响因子：
45.3
通讯作者：
Montorsi, Francesco
中科院分区：
文献类型：
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作者：
Necchi, Andrea;Anichini, Andrea;Montorsi, Francesco
目的确定派姆单抗作为肌肉浸润性膀胱癌（MIBC）根治性膀胱切除术（RC）前新辅助免疫治疗的活性，其中标准顺铂为基础的化疗很少使用。在PURE-01研究中，患者主要为尿路上皮癌组织学和临床(c)T3bN0期肿瘤。他们在RC前每3周接受3个周期200毫克的派姆单抗治疗。意向治疗人群的主要终点是病理完全缓解（pT0）。生物标志物分析包括程序性死亡配体1 （PD-L1）表达，使用联合阳性评分（CPS； Dako 22C3 pharmDx测定）、基因组测序（FoundationONE测定）和免疫基因表达测定。结果从2017年2月至2018年3月入组50例患者。27例（54%）为cT3肿瘤，21例（42%）为cT2肿瘤，2例（4%）为cT2- 3n1肿瘤。1例（2%）患者出现3级转氨酶升高并停止使用派姆单抗。所有患者均接受RC；pT0患者21例（42%;95% CI, 28.2% ~ 56.8%）。作为次要终点，降级到pT
PurposeTo determine the activity of pembrolizumab as neoadjuvant immunotherapy before radical cystectomy (RC) for muscle-invasive bladder carcinoma (MIBC) for which standard cisplatin-based chemotherapy is poorly used.Patients and MethodsIn the PURE-01 study, patients had a predominant urothelial carcinoma histology and clinical (c)T3bN0 stage tumor. They received three cycles of pembrolizumab 200 mg every 3 weeks before RC. The primary end point in the intention-to-treat population was pathologic complete response (pT0). Biomarker analyses included programmed death-ligand 1 (PD-L1) expression using the combined positive score (CPS; Dako 22C3 pharmDx assay), genomic sequencing (FoundationONE assay), and an immune gene expression assay.ResultsFifty patients were enrolled from February 2017 to March 2018. Twenty-seven patients (54%) had cT3 tumor, 21 (42%) cT2 tumor, and two (4%) cT2-3N1 tumor. One patient (2%) experienced a grade 3 transaminase increase and discontinued pembrolizumab. All patients underwent RC; there were 21 patients with pT0 (42%; 95% CI, 28.2% to 56.8%). As a secondary end point, downstaging to pT