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Systematic Review of Immune Checkpoint Inhibition in Urological Cancers
European Urology ( IF 25.3 ) Pub Date : 2017-06-20 , DOI: 10.1016/j.eururo.2017.06.012
Maud Rijnders , Ronald de Wit , Joost L. Boormans , Martijn P.J. Lolkema , Astrid A.M. van der Veldt

Context

In patients with advanced and metastatic urological cancers, clinical outcome may be improved by immune checkpoint inhibitors (ICIs).

Objective

To systematically review relevant literature on efficacy and safety of ICIs in patients with advanced and metastatic urothelial cell cancer (UCC), renal cell cancer (RCC), and prostate cancer.

Evidence acquisition

Relevant databases, including Medline, Embase, and the Cochrane Library, were searched up to March 16, 2017. A narrative review of randomized clinical trials (RCTs) was performed.

Evidence synthesis

Six RCTs were included for the systematic review. In platinum-pretreated UCC, efficacy of pembrolizumab was superior to chemotherapy, with longer median overall survival (OS; 10.3 vs 7.4 mo), a higher objective response rate (ORR; 21.1% vs 11.4%, p = 0.001), and a lower adverse event rate (60.9% vs 90.2%). Three RCTs assessed the safety and efficacy of nivolumab in advanced RCC. The median OS (25.0 vs 19.6 mo) and the ORR (25% vs 5%) were higher in patients treated with nivolumab compared with second-line everolimus. In all three studies, the safety profile of nivolumab was favorable. In patients with metastatic castration-resistant prostate cancer, two RCTs were identified, which did not show significant benefits for ipilimumab over placebo. In UCC and RCC, there was no conclusive association between programmed cell death receptor ligand 1 (PD-L1) expression in tumor tissue and clinical outcome during pembrolizumab and nivolumab treatment, respectively.

Conclusion

In metastatic UCC and RCC, pembrolizumab and nivolumab have superior efficacy and safety to second-line chemotherapy and everolimus, respectively. No beneficial effect of ipilimumab was observed in prostate cancer patients. PD-L1 expression status is currently not suitable as a predictive marker for treatment outcome.

Patient summary

Immune checkpoint inhibitors are able to reactivate the immune system against tumor cells. In second-line setting, pembrolizumab and nivolumab are safe and confer survival benefit in advanced urothelial cell and renal cell cancer, respectively.



中文翻译:

泌尿系统肿瘤免疫检查点抑制的系统评价

语境

在患有晚期和转移性泌尿系癌症的患者中,免疫检查点抑制剂(ICI)可能会改善临床结局。

客观的

为了系统地回顾有关ICI在晚期和转移性尿路上皮细胞癌(UCC),肾细胞癌(RCC)和前列腺癌患者中的功效和安全性的相关文献。

取证

截至2017年3月16日,对相关数据库(包括Medline,Embase和Cochrane库)进行了搜索。对随机临床试验(RCT)进行了叙述性综述。

证据综合

纳入了六个RCT,用于系统评价。在铂预处理的UCC中,派姆单抗的疗效优于化疗,中位总生存期更长(OS; 10.3 vs 7.4 mo),更高的客观缓解率(ORR; 21.1%vs 11.4%,p = 0.001)和更低的不良事件发生率(60.9%对90.2%)。三个RCT评估了nivolumab在晚期RCC中的安全性和有效性。与二线依维莫司相比,用nivolumab治疗的患者的中位OS(25.0 vs 19.6 mo)和ORR(25%vs 5%)更高。在所有三项研究中,nivolumab的安全性均良好。在具有转移性去势抵抗性前列腺癌的患者中,确定了两个RCT,与安慰剂相比,依匹莫单抗没有明显的益处。在UCC和RCC中,在pembrolizumab和nivolumab治疗期间,肿瘤组织中程序性细胞死亡受体配体1(PD-L1)表达与临床结局之间没有结论性关联。

结论

在转移性UCC和RCC中,pembrolizumab和nivolumab分别具有优于二线化疗和依维莫司的疗效和安全性。在前列腺癌患者中未观察到伊立木单抗的有益作用。目前,PD-L1表达状态不适合作为治疗结果的预测指标。

病人总结

免疫检查点抑制剂能够重新激活针对肿瘤细胞的免疫系统。在二线治疗中,pembrolizumab和nivolumab是安全的,分别在晚期尿路上皮细胞和肾细胞癌中具有生存优势。

更新日期:2017-06-20
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