在转移性尿路上皮癌患者中，先前接受过恩杂鲁胺治疗后使用戈沙妥珠单抗的真实世界临床结局。

Real-world clinical outcomes of sacituzumab govitecan after prior exposure to enfortumab vedotin in patients with metastatic urothelial carcinoma.

作者信息

Sternschuss M, Toumbacaris N, Das J P, Powles T, Kotecha R R, Laccetti A L, Xiao H, Feld E, McHugh D J, Keegan N M, Bajorin D F, Funt S A, Shah N J, Iyer G, Aggen D H, Teo M Y, Ostrovnaya I, Rosenberg J E

机构信息

Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, USA; Davidoff Cancer Center, Rabin Medical Center, Petah Tikva, Israel.

Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, USA.

出版信息

ESMO Open. 2025 Jun;10(6):105305. doi: 10.1016/j.esmoop.2025.105305. Epub 2025 Jun 5.

DOI:10.1016/j.esmoop.2025.105305

PMID:40479863

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12173038/

Abstract

BACKGROUND

Sacituzumab govitecan (SG) is an antibody-drug conjugate associated with clinically meaningful responses as advanced-line treatment of metastatic urothelial carcinoma (mUC). Practically, SG has been most commonly used in the post-enfortumab vedotin (EV) setting, but data are scarce regarding the efficacy in this population, including the negative phase III study that enrolled mostly EV-naive patients.

PATIENTS AND METHODS

This was a single-center retrospective cohort of patients with mUC treated with SG after prior exposure to EV between April 2021 and November 2023. Clinical data were collected by chart review. Response to SG [complete response (CR), partial response (PR) and stable disease (SD)] was the primary endpoint and confirmed by radiologist evaluation using RECIST v1.1. Progression-free survival (PFS) and overall survival (OS) were calculated using the Kaplan-Meier method.

RESULTS

A total of 82 patients were identified. Median age was 71 years, 70% were male, 37% had upper tract primaries and 93% had visceral disease. The median number of prior treatment lines was 3 (range 1-8), and 68% received SG directly after EV. The observed response rate (ORR) was 11% [95% confidence interval (CI) 5.2% to 20%], with no CRs; median PFS was 2.1 months (95% CI 1.9-2.5 months), and median OS was 6.0 months (95% CI 4.5-6.9 months). There was no association between response to EV and outcomes with SG. Sequencing SG directly after EV was associated with improved ORR (P = 0.024) and PFS (hazard ratio 0.46, P = 0.019) but not OS. Primary prophylactic granulocyte colony-stimulating factor was administered in 70% of patients and was not associated with lower risk of neutropenia. G3-4 neutropenia and anemia each occurred in 36% of patients. Adverse events leading to SG discontinuation occurred in 5% of patients; there were no treatment-related deaths.

CONCLUSIONS

SG resulted in limited clinical efficacy in our large cohort of real-world advanced mUC patients with prior exposure to EV.

摘要

背景

戈沙妥珠单抗（SG）是一种抗体药物偶联物，作为转移性尿路上皮癌（mUC）的晚期治疗药物，具有临床意义的疗效。实际上，SG最常用于恩扎妥昔单抗（EV）治疗之后，但关于该人群疗效的数据较少，包括一项主要纳入未接受过EV治疗患者的III期阴性研究。

患者和方法

这是一项单中心回顾性队列研究，纳入了2021年4月至2023年11月期间在先前接受EV治疗后接受SG治疗的mUC患者。通过病历审查收集临床数据。对SG的反应[完全缓解（CR）、部分缓解（PR）和疾病稳定（SD）]是主要终点，并由放射科医生使用RECIST v1.1进行评估确认。无进展生存期（PFS）和总生存期（OS）采用Kaplan-Meier方法计算。

结果

共纳入82例患者。中位年龄为71岁，70%为男性，37%为上尿路原发肿瘤，93%有内脏疾病。既往治疗线数的中位数为3（范围1 - 8），68%的患者在EV治疗后直接接受SG治疗。观察到的缓解率（ORR）为11%[95%置信区间（CI）5.2%至20%]，无CR；中位PFS为2.1个月（95% CI 1.9 - 2.5个月），中位OS为6.0个月（95% CI 4.5 - 6.9个月）。对EV的反应与SG治疗的结果之间无关联。在EV治疗后直接序贯使用SG与ORR改善（P = 0.024）和PFS改善（风险比0.46，P = 0.019）相关，但与OS无关。70%的患者接受了一级预防性粒细胞集落刺激因子治疗，且与较低的中性粒细胞减少风险无关。36%的患者发生3 - 4级中性粒细胞减少和贫血。5%的患者发生导致SG停药的不良事件；无治疗相关死亡。