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转移性尿路上皮癌全身治疗的范式转变——抗体药物偶联物(ADCs)和成纤维细胞生长因子受体(FGFR)抑制剂

[Paradigm shift in systemic therapy for metastatic urothelial carcinoma-antibody-drug conjugates (ADCs) and fibroblast growth factor receptor (FGFR) inhibitors].

作者信息

Casuscelli Jozefina, von Amsberg Gunhild, Retz Margitta

机构信息

Urologische Klinik und Poliklinik, Campus Großhadern, Klinikum der Universität München, Marchioninistr. 15, 81337, München, Deutschland.

Zentrum für Onkologie und Martini-Klinik, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Deutschland.

出版信息

Urologie. 2024 Oct;63(10):1002-1010. doi: 10.1007/s00120-024-02440-1. Epub 2024 Sep 5.

Abstract

BACKGROUND

Patients with locally advanced or metastatic urothelial carcinoma face a poor prognosis. Standard first-line treatment involves platinum-based combinations followed by avelumab maintenance therapy. Follow-up therapies include enfortumab vedotin, vinflunine, and taxanes.

OBJECTIVE

To analyze new drug combinations in first-line and follow-up treatment for metastatic urothelial carcinoma concerning their clinical relevance, toxicities, and novel treatment sequences.

MATERIALS AND METHODS

Analysis of new study data from EV-302/KN-A39 (enfortumab vedotin and pembrolizumab) and CheckMate-901 (nivolumab and gemcitabine-cisplatin) for untreated metastatic patients as well as TROPHY-U-01 (sacituzumab govitecan) and THOR (erdafitinib) for later lines.

RESULTS

The new standard in first-line treatment for metastatic urothelial carcinoma is the combination of enfortumab vedotin and pembrolizumab. For cisplatin-eligible patients with contraindications to enfortumab vedotin, the combination of nivolumab and gemcitabine-cisplatin offers an alternative. Erdafitinib presents a new biomarker-based option in the follow-up treatment of metastatic urothelial carcinoma.

CONCLUSION

These novel combinations are revolutionizing the treatment standard for metastatic urothelial carcinoma and necessitate a new approach to managing side effects.

摘要

背景

局部晚期或转移性尿路上皮癌患者预后较差。标准一线治疗包括铂类联合方案,随后是阿维鲁单抗维持治疗。后续治疗包括恩杂鲁胺、长春氟宁和紫杉烷类。

目的

分析转移性尿路上皮癌一线和后续治疗中的新药联合方案,探讨其临床相关性、毒性及新的治疗顺序。

材料与方法

分析来自EV-302/KN-A39(恩杂鲁胺和帕博利珠单抗)和CheckMate-901(纳武利尤单抗和吉西他滨-顺铂)针对未治疗的转移性患者的新研究数据,以及TROPHY-U-01(戈沙妥珠单抗)和THOR(厄达替尼)针对后续治疗线的数据。

结果

转移性尿路上皮癌一线治疗的新标准是恩杂鲁胺和帕博利珠单抗联合。对于有恩杂鲁胺禁忌证的顺铂适用患者,纳武利尤单抗和吉西他滨-顺铂联合提供了一种替代方案。厄达替尼在转移性尿路上皮癌后续治疗中提供了一种基于新生物标志物选择。

结论

这些新的联合方案正在彻底改变转移性尿路上皮癌的治疗标准,需要一种新的方法来管理副作用。

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