与在检查点抑制剂治疗后转移性尿路上皮癌中重新使用化疗相比，恩杂鲁胺对其有持久反应。
Durable Response to Enfortumab Vedotin Compared to Re-challenging Chemotherapy in Metastatic Urothelial Carcinoma After Checkpoint Inhibitors.
作者信息
Uchimoto Taizo, Tsuchida Shuya, Komura Kazumasa, Fukuokaya Wataru, Adachi Takahiro, Hirasawa Yosuke, Hashimoto Takeshi, Yoshizawa Atsuhiko, Saruta Masanobu, Hashimoto Mamoru, Higashio Takuya, Matsuda Takuya, Nishimura Kazuki, Tsujino Takuya, Nakamura Ko, Fukushima Tatsuo, Nishio Kyosuke, Yamamoto Shutaro, Iwatani Kosuke, Urabe Fumihiko, Mori Keiichiro, Yanagisawa Takafumi, Tsuduki Shunsuke, Takahara Kiyoshi, Inamoto Teruo, Miki Jun, Fujita Kazutoshi, Kimura Takahiro, Ohno Yoshio, Shiroki Ryoichi, Uemura Hirotsugu, Azuma Haruhito
机构信息
Department of Urology, Osaka Medical and Pharmaceutical University, 2-7 Daigaku-machi, Takatsuki, Osaka, 569-8686, Japan.
Department of Urology, The Jikei University School of Medicine, 3-25-8, Nishi-shimbashi, Minato-ku, Tokyo, 105-8461, Japan.
出版信息
Target Oncol. 2024 May;19(3):401-410. doi: 10.1007/s11523-024-01047-y. Epub 2024 Mar 28.
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.
背景
恩沃利单抗（EV）是一种靶向Nectin-4的抗体偶联药物，已用于在检查点抑制剂（CPI）治疗后病情进展的转移性尿路上皮癌（mUC）患者。在CPI治疗出现疾病进展（PD）后，常选择铂类药物重新挑战化疗以及在疾病进展后继续使用CPI，多项研究表明重新挑战化疗具有良好的治疗效果。在真实世界的临床实践中，比较EV和重新挑战化疗的证据很少。
目的
旨在揭示mUC患者中EV、重新挑战化疗以及在疾病进展后继续使用CPI的真实世界治疗结果。
患者和方法
使用了一个多机构的数据集，其中包含350例接受CPI治疗的mUC患者。评估总生存期（OS）、无进展生存期（PFS）、客观缓解率（ORR）和缓解持续时间（DOR）以比较各治疗组。
结果
109例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%。帕博利珠单抗治疗出现PD后的OS在三组之间存在显著差异，在疾病进展后继续使用帕博利珠单抗、重新挑战化疗和EV组中，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和重新挑战化疗之间的OS（p = 0.124）、PFS（p = 0.936）和ORR（p = 0.816）均无差异。值得注意的是，在达到客观缓解的患者中，EV组的DOR显著长于重新挑战化疗组（中位时间分别为11个月和5个月，p = 0.049）。对于OS，差异无统计学意义（EV组和重新挑战化疗组分别为27个月和11个月：p = 0.05）。
结论
在我们的真实世界分析中，观察到与重新挑战化疗以及在疾病进展后继续使用帕博利珠单抗相比，EV对患者生存具有更好的效果，这归因于尽管EV的ORR与重新挑战化疗相似，但其治疗中的DOR持久。
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