Durable Response to Enfortumab Vedotin Compared to Re-challenging Chemotherapy in Metastatic Urothelial Carcinoma After Checkpoint Inhibitors.

IF 4.4 3区医学 Q2 ONCOLOGY

Targeted Oncology Pub Date : 2024-05-01 Epub Date: 2024-03-28 DOI:10.1007/s11523-024-01047-y

Taizo Uchimoto, Shuya Tsuchida, Kazumasa Komura, Wataru Fukuokaya, Takahiro Adachi, Yosuke Hirasawa, Takeshi Hashimoto, Atsuhiko Yoshizawa, Masanobu Saruta, Mamoru Hashimoto, Takuya Higashio, Takuya Matsuda, Kazuki Nishimura, Takuya Tsujino, Ko Nakamura, Tatsuo Fukushima, Kyosuke Nishio, Shutaro Yamamoto, Kosuke Iwatani, Fumihiko Urabe, Keiichiro Mori, Takafumi Yanagisawa, Shunsuke Tsuduki, Kiyoshi Takahara, Teruo Inamoto, Jun Miki, Kazutoshi Fujita, Takahiro Kimura, Yoshio Ohno, Ryoichi Shiroki, Hirotsugu Uemura, Haruhito Azuma

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引用次数: 0

Abstract

Background: Enfortumab vedotin (EV), an antibody-drug conjugate targeting Nectin-4, has been used for patients with metastatic urothelial carcinoma (mUC) after progressing on checkpoint inhibitors (CPIs). Re-challenging chemotherapy with platinum agents and continuing CPIs beyond progressive disease (PD) have often been chosen following PD on CPIs, and several studies indicate favorable treatment effects of re-challenging chemotherapy. There is little evidence for comparing EV and re-challenging chemotherapy in real-world clinical practice.

Objective: The aim was to reveal the real-world treatment outcomes of EV, re-challenging chemotherapy, and continuing CPIs beyond PD in mUC patients.

Patients and methods: A multi-institutional dataset of 350 mUC patients treated with CPIs was utilized. Overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and duration of response (DOR) were evaluated to compare the treatment arms.

Results: One hundred and nine mUC patients were treated with EV with a median follow-up of 6.4 months. The ORR and disease control rate (DCR) were 48% and 70%, respectively. The OS from PD on pembrolizumab exhibited significant differences among the three groups, with a median OS of 8, 14, and 29 months in continuing pembrolizumab beyond PD, re-challenging chemotherapy, and EV, respectively. When comparing the survival outcomes from the initiation of the treatment, there is neither a difference in OS (p = 0.124), PFS (p = 0.936), nor ORR (p = 0.816) between EV and re-challenging chemotherapy. Notably, the DOR in patients who achieved an objective response was significantly longer in the EV group than the re-challenging chemotherapy group (a median of 11 and 5 months, p = 0.049). For OS, the difference was not statistically significant (27 and 11 months in EV and re-challenging chemotherapy, respectively: p = 0.05).

Conclusions: A superior effect of EV on patient survival compared to re-challenging chemotherapy and continuing pembrolizumab beyond PD was observed in our real-world analysis, which is attributed to the durable DOR in EV treatment despite the similar ORR to re-challenging chemotherapy.

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检查点抑制剂后转移性尿路上皮癌患者对恩福单抗维多汀的持久反应与再次化疗相比

背景：恩福单抗维多汀（EV）是一种靶向Nectin-4的抗体药物共轭物，已被用于治疗使用检查点抑制剂（CPIs）后病情进展的转移性尿路上皮癌（mUC）患者。在使用检查点抑制剂（CPIs）治疗进展期后，患者通常会选择再次使用铂类药物进行化疗，并在疾病进展期（PD）后继续使用CPIs。在实际临床实践中，几乎没有证据可以比较EV和再挑战化疗：目的：揭示EV、再挑战化疗和继续CPIs在mUC患者PD后的实际治疗效果：患者和方法：我们利用了一个包含350名接受CPIs治疗的mUC患者的多机构数据集。对总生存期（OS）、无进展生存期（PFS）、客观反应率（ORR）和反应持续时间（DOR）进行了评估，以比较各治疗方案：结果：109名mUC患者接受了EV治疗，中位随访时间为6.4个月。ORR和疾病控制率（DCR）分别为48%和70%。三组患者从开始使用pembrolizumab起的OS表现出显著差异，PD后继续使用pembrolizumab、重新接受化疗和EV的中位OS分别为8个月、14个月和29个月。在比较治疗开始后的生存结果时，EV组和再次挑战化疗组的OS（p = 0.124）、PFS（p = 0.936）和ORR（p = 0.816）均无差异。值得注意的是，EV组获得客观应答的患者的DOR明显长于再次挑战化疗组（中位数分别为11个月和5个月，p = 0.049）。在OS方面，差异无统计学意义（EV组和再次接受化疗组分别为27个月和11个月：P = 0.05）：在我们的真实世界分析中观察到，EV对患者生存期的影响优于重新接受化疗和在PD后继续使用pembrolizumab，这归因于EV治疗的持久DOR，尽管其ORR与重新接受化疗相似。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Targeted Oncology 医学-肿瘤学

CiteScore

8.40

自引率

3.70%

发文量

审稿时长

>12 weeks

期刊介绍： Targeted Oncology addresses physicians and scientists committed to oncology and cancer research by providing a programme of articles on molecularly targeted pharmacotherapy in oncology. The journal includes: Original Research Articles on all aspects of molecularly targeted agents for the treatment of cancer, including immune checkpoint inhibitors and related approaches. Comprehensive narrative Review Articles and shorter Leading Articles discussing relevant clinically established as well as emerging agents and pathways. Current Opinion articles that place interesting areas in perspective. Therapy in Practice articles that provide a guide to the optimum management of a condition and highlight practical, clinically relevant considerations and recommendations. Systematic Reviews that use explicit, systematic methods as outlined by the PRISMA statement. Adis Drug Reviews of the properties and place in therapy of both newer and established targeted drugs in oncology.