Immune Checkpoint Inhibitors for the Treatment of Bladder Cancer.
Immune Checkpoint Inhibitors for the Treatment of Bladder Cancer.
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DOI：
10.3390/cancers13010131
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发表时间：
2021-01-03
期刊：
影响因子：
5.2
通讯作者：
Montironi R
中科院分区：
文献类型：
--
作者：
Lopez-Beltran A;Cimadamore A;Blanca A;Massari F;Vau N;Scarpelli M;Cheng L;Montironi R
在这篇综述中，我们检查了免疫检查点抑制剂在转移性尿路上皮癌患者中的相关临床试验结果。我们还关注了免疫疗法在辅助和新辅助治疗中的潜力，或作为药物组合的一部分。最后，我们简要回顾了免疫检查点抑制剂反应生物标志物的现状，如程序性死亡配体1（PD-L1）表达，肿瘤突变负荷，膀胱癌的分子亚型和免疫基因表达谱。许多免疫检查点抑制剂（ICI）已被批准作为顺铂不合格患者的一线治疗或膀胱转移性尿路上皮癌（mUC）患者的二线治疗。大约30%的mUC患者将对ICI免疫治疗有反应。通过免疫组织化学检测的程序性死亡配体1（PD-L1）表达似乎可以预测mUC患者对免疫检查点抑制剂的应答，这得到了与大多数临床试验中观察到的应答相关的客观缓解率（ORR）和总生存期（OS）的支持。Pembrolizumab是一种抗PD-1抗体，在一项用于mUC二线治疗的随机化III期研究中，其OS优于化疗。Nivolumab是一种PD-1抗体，与对照组相比，也显示出OS获益。靶向PD-L1的Atezolizumab、Durvalumab和Avelumab抗体也已获批作为mUC的二线治疗药物，在选定患者中的持续缓解超过1年。Atezolizumab和Pembrolizumab也被批准用于不适合顺铂治疗的患者的一线治疗。关注ICI在辅助或新辅助治疗中的效用，或与化疗联合使用，是一些正在进行的试验的基础。正如当前文献所强调的，非常需要鉴定临床上有用的生物标志物（单独或联合），以确定mUC患者的最佳ICI治疗。在这篇综述中，我们检查了在mUC患者中单独或作为药物组合的一部分的ICI的相关临床试验结果;重点也放在辅助和新辅助治疗上。还简要回顾了对ICI反应的选定生物标志物（包括抗PD-L1免疫组织化学）的当前情况。
In this review, we examined relevant clinical trial results with immune checkpoint inhibitors in patients with metastatic urothelial cancer. We also focused on the potential of immunotherapy in the adjuvant and neoadjuvant setting or as part of drug combinations. Finally, we briefly review the current landscape of biomarkers of response to immune checkpoint inhibitors, such as programmed death-ligand 1 (PD-L1) expression, tumor mutation burden, molecular subtypes of bladder cancer, and immune-gene expression profiling. A number of immune checkpoint inhibitors (ICIs) have been approved as first-line therapy in case of cisplatin-ineligible patients or as second-line therapy for patients with metastatic urothelial carcinoma (mUC) of the bladder. About 30% of patients with mUC will respond to ICIs immunotherapy. Programmed death-ligand 1 (PD-L1) expression detected by immunohistochemistry seems to predict response to immune checkpoint inhibitors in patients with mUC as supported by the objective response rate (ORR) and overall survival (OS) associated with the response observed in most clinical trials. Pembrolizumab, an anti-PD-1 antibody, demonstrated better OS respective to chemotherapy in a randomized phase 3 study for second-line treatment of mUC. Nivolumab, a PD-1 antibody, also demonstrated an OS benefit when compared to controls. Atezolizumab, Durvalumab, and Avelumab antibodies targeting PD-L1 have also received approval as second-line treatments for mUC with durable response for more than 1 year in selected patients. Atezolizumab and Pembrolizumab also received approval for first-line treatment of patients that are ineligible for cisplatin. A focus on the utility of ICIs in the adjuvant or neoadjuvant setting, or as combination with chemotherapy, is the basis of some ongoing trials. The identification of a clinically useful biomarker, single or in association, to determine the optimal ICIs treatment for patients with mUC is very much needed as emphasized by the current literature. In this review, we examined relevant clinical trial results with ICIs in patients with mUC alone or as part of drug combinations; emphasis is also placed on the adjuvant and neoadjuvant setting. The current landscape of selected biomarkers of response to ICIs including anti-PD-L1 immunohistochemistry is also briefly reviewed.
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影响因子：
2.1
作者：
Faraj SF;Munari E;Guner G;Taube J;Anders R;Hicks J;Meeker A;Schoenberg M;Bivalacqua T;Drake C;Netto GJ
通讯作者：
Netto GJ
影响因子：
5.6
作者：
Bednova O;Leyton JV
通讯作者：
Leyton JV
影响因子：
23.4
作者：
Galsky, Matthew D.;Wang, Huan;Uzilov, Andrew V.
通讯作者：
Uzilov, Andrew V.
影响因子：
8.4
作者：
Eckstein, Markus;Erben, Philipp;Erlmeier, Franziska
通讯作者：
Erlmeier, Franziska
影响因子：
4.4
作者：
Allard, David;Chrobak, Pavel;Stagg, John
通讯作者：
Stagg, John