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转移性尿路上皮癌的转换维持治疗

Switch Maintenance Therapy for Metastatic Urothelial Carcinoma.

作者信息

Ahmed Ramsha, Gupta Shilpa

机构信息

Department of Hematology and Oncology, Cleveland Clinic, Cleveland, OH, USA.

出版信息

Bladder Cancer. 2022 Dec 14;8(4):359-369. doi: 10.3233/BLC-220030. eCollection 2022.

Abstract

INTRODUCTION

While switch maintenance therapy is being increasingly investigated in solid tumors, it is a standard in only a few. We conducted a systematic review on switch maintenance therapy for metastatic urothelial carcinoma.

EVIDENCE ACQUISITION

In this systematic review, we conducted a literature search in PubMed and Cochrane databases up to 2021, based on PRISMA statement guidelines. One hundred and fifty eight articles were identified and after a three-step selection process and six articles, using different agents were included in evidence synthesis. The primary end points were effect on overall survival, progression free survival, safety and tolerability.

EVIDENCE SYNTHESIS

In the pre-immunotherapy era, targeted therapies like sunitinib, lapatinib and vinflunine were studied as switch maintenance therapy in metastatic urothelial carcinoma but did not show any overall survival benefit. Use of anti-PD-1/PD-L1 agents have shown promise as switch maintenance therapy; pembrolizumab showed improvement in progression free survival in a phase 2 trial and avelumab showed improvement in overall survival and progression free survival in the phase 3 JAVELIN Bladder 100 trial.

CONCLUSION

Immunotherapy with anti-PD-1/PD-L1 agents has emerged as an effective switch maintenance strategy in patients with metastatic urothelial carcinoma. Intensification of the immunotherapy backbone in this setting can potentially further enhance outcomes. Emerging evidence shows a potential role of Poly (ADP-ribose) polymerase (PARP) inhibitors in this setting as well. Results from ongoing and planned studies will help us understand which switch maintenance approaches would be most effective for improving outcomes in metastatic urothelial carcinoma.

摘要

引言

虽然转换维持治疗在实体瘤中的研究日益增多,但只有少数几种肿瘤将其作为标准治疗方法。我们对转移性尿路上皮癌的转换维持治疗进行了系统评价。

证据获取

在本系统评价中,我们根据PRISMA声明指南,在截至2021年的PubMed和Cochrane数据库中进行了文献检索。共识别出158篇文章,经过三步筛选过程,最终纳入6篇使用不同药物的文章进行证据综合分析。主要终点为对总生存期、无进展生存期、安全性和耐受性的影响。

证据综合

在免疫治疗时代之前,舒尼替尼、拉帕替尼和长春氟宁等靶向治疗药物曾作为转移性尿路上皮癌的转换维持治疗进行研究,但未显示出任何总生存期获益。抗PD-1/PD-L1药物作为转换维持治疗已显示出前景;帕博利珠单抗在一项2期试验中显示无进展生存期有所改善,阿维鲁单抗在3期JAVELIN Bladder 100试验中显示总生存期和无进展生存期均有所改善。

结论

抗PD-1/PD-L1药物免疫治疗已成为转移性尿路上皮癌患者有效的转换维持策略。在这种情况下强化免疫治疗基础可能会进一步改善治疗效果。新出现的证据也表明聚(ADP-核糖)聚合酶(PARP)抑制剂在这种情况下也具有潜在作用。正在进行和计划中的研究结果将有助于我们了解哪种转换维持方法对改善转移性尿路上皮癌的治疗效果最有效。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa5f/11181790/1f70df9df799/blc-8-blc220030-g001.jpg

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