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免疫检查点抑制剂在尿路上皮癌治疗中的应用

Immune Checkpoint Inhibitors in the Management of Urothelial Carcinoma.

作者信息

Patel Aakash, Bisno Daniel I, Patel Hiren V, Ghodoussipour Saum, Saraiya Biren, Mayer Tina, Singer Eric A

机构信息

Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ 08901, USA.

Section of Urologic Oncology, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ 08903, USA.

出版信息

J Cancer Immunol (Wilmington). 2021;3(2):115-136. doi: 10.33696/cancerimmunol.3.047.

Abstract

Urothelial carcinoma is one of the most common cancers in the United States, yet outcomes are historically suboptimal. Since 2016, the approval of five programmed cell death 1 and programmed death-ligand 1 immune checkpoint inhibitors for locally advanced and metastatic urothelial carcinoma has led to improved oncologic outcomes for many patients in the second-line setting. Two checkpoint inhibitors, pembrolizumab and atezolizumab subsequently earned approval for first-fine therapy with restricted indications. More recently, pembrolizumab was approved for bacillus Calmette-Guérin-unresponsive high-risk non-muscle invasive bladder cancer, opening the door for other immune checkpoint inhibitors to be integrated into treatment in earlier disease stages. Recent bacillus Calmette-Guérin shortages have highlighted the need for alternative treatment options for patients with non-muscle invasive bladder cancer. Currently, there are no FDA-approved checkpoint inhibitors for non-metastatic muscle-invasive bladder cancer. Furthermore, many patients are ineligible for standard cisplatin-based chemotherapy regimens. Numerous ongoing clinical trials are employing immune checkpoint inhibitors for muscle-invasive bladder cancer patients in the neoadjuvant, adjuvant, perioperative, and bladder-sparing setting. Although up to 10% of urothelial carcinoma tumors arise in the upper urinary tract, few studies are designed for this population. We highlight the need for more trials designed for patients with upper tract disease. Overall, there are numerous clinical trials investigating the safety and efficacy of immune checkpoint inhibitors in all stages of disease as single-agents and combined with dual-immune checkpoint inhibition, chemotherapy, radiotherapy, and other pharmacologic agents. As the field continues to evolve rapidly, we aim to provide an overview of recent and ongoing immunotherapy clinical trials in urothelial carcinoma.

摘要

尿路上皮癌是美国最常见的癌症之一,但其历史治疗效果一直欠佳。自2016年以来,五种程序性细胞死亡蛋白1(PD-1)和程序性死亡配体1(PD-L1)免疫检查点抑制剂获批用于局部晚期和转移性尿路上皮癌,使许多二线治疗患者的肿瘤学结局得到改善。两种检查点抑制剂,帕博利珠单抗和阿替利珠单抗随后获批用于一线治疗,但有严格的适应症限制。最近,帕博利珠单抗获批用于卡介苗无反应的高危非肌层浸润性膀胱癌,为其他免疫检查点抑制剂在疾病早期阶段的治疗应用打开了大门。近期卡介苗短缺凸显了非肌层浸润性膀胱癌患者需要替代治疗方案。目前,尚无美国食品药品监督管理局(FDA)批准的用于非转移性肌层浸润性膀胱癌的检查点抑制剂。此外,许多患者不符合基于顺铂的标准化疗方案。众多正在进行的临床试验正在新辅助、辅助、围手术期和保留膀胱的治疗中,将免疫检查点抑制剂用于肌层浸润性膀胱癌患者。尽管高达10%的尿路上皮癌肿瘤发生在上尿路,但针对该人群的研究很少。我们强调需要开展更多针对上尿路疾病患者的试验。总体而言,有许多临床试验正在研究免疫检查点抑制剂作为单一药物以及与双重免疫检查点抑制、化疗、放疗和其他药物联合使用时,在疾病各个阶段的安全性和有效性。随着该领域的快速发展,我们旨在概述尿路上皮癌近期和正在进行的免疫治疗临床试验。

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