Sacituzumab govitecan治疗晚期尿路上皮癌：tropic -04，一项III期随机试验。

IF 56.7 1区医学 Q1 ONCOLOGY

Annals of Oncology Pub Date : 2025-02-11 DOI:10.1016/j.annonc.2025.01.011

T. Powles , S. Tagawa , C. Vulsteke , M. Gross-Goupil , S.H. Park , A. Necchi , M. De Santis , I. Duran , R. Morales-Barrera , J. Guo , C.N. Sternberg , J. Bellmunt , P.J. Goebell , M. Kovalenko , F. Boateng , M. Sierecki , L. Wang , C.S. Sima , J. Waldes , Y. Loriot , P. Grivas

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引用次数: 0

摘要

背景：Sacituzumab govitecan （SG）是一种trop -2导向的抗体-药物偶联物，在预处理的晚期尿路上皮癌（aUC）的II期TROPHY-U-01研究中显示出疗效和可控制的毒性。我们报告了预处理aUC的全球开放标签随机III期troics -04研究（NCT04527991）的最终分析结果。患者和方法：先前接受铂类化疗和检查点抑制剂治疗的aUC患者病情进展，随机1:1接受SG或医生选择的治疗(TPC；紫杉醇、多西紫杉醇或长春氟宁)。主要终点是总生存期（OS）。次要终点包括研究者和盲法独立委员会审查的无进展生存期（PFS）和客观缓解率（ORR），以及安全性。结果：总体而言，711例患者被随机分组。中位随访9.2个月后，主要终点未达到[SG vs TPC的中位OS: 10.3个月vs 9.0个月，风险比（HR） 0.86, 95%可信区间（CI） 0.73-1.02, P = 0.087]。SG和TPC的中位PFS分别为4.2个月和3.6个月（HR 0.86, 95% CI 0.72-1.03）；ORR （95% CI）分别为23%（18% ~ 27%）和14%（10% ~ 18%）。SG最常见的≥3级治疗相关不良事件（TRAE）是中性粒细胞减少（35%，其中12%为发热性中性粒细胞减少）。≥3级trae发生率（67% vs 35%）和5级治疗不良事件发生率(teae；7% vs 2%)， SG组高于TPC组。在SG组中，16/25的5级teae是中性粒细胞减少的感染，主要发生在具有发热性中性粒细胞减少的多种危险因素的患者的治疗早期。原发性预防性粒细胞集落刺激因子（G-CSF）在SG和TPC患者中的使用率分别为21%和22%。结论：与预处理aUC的TPC相比，SG并没有导致OS或PFS的显著改善，尽管SG活性可以通过更高的ORR来证明。SG的早期毒性相关并发症可能影响疗效结果。

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Sacituzumab govitecan in advanced urothelial carcinoma: TROPiCS-04, a phase III randomized trial

Background

Sacituzumab govitecan (SG), a Trop-2-directed antibody–drug conjugate, demonstrated efficacy and manageable toxicity in the phase II TROPHY-U-01 study in pretreated advanced urothelial carcinoma (aUC). We report the results from final analysis of the global open-label randomized phase III TROPiCS-04 study (NCT04527991) in pretreated aUC.

Patients and methods

Patients with aUC whose disease had progressed on prior platinum-based chemotherapy and checkpoint inhibitor therapy were randomized 1 : 1 to receive SG or treatment of physician’s choice (TPC; paclitaxel, docetaxel, or vinflunine). The primary endpoint was overall survival (OS). Secondary endpoints included progression-free survival (PFS) and objective response rate (ORR) by investigator and blinded independent committee review, as well as safety.

Results

Overall, 711 patients were randomized. After a median follow-up of 9.2 months, the primary endpoint was not met [median OS for SG versus TPC: 10.3 months versus 9.0 months, hazard ratio (HR) 0.86, 95% confidence interval (CI) 0.73-1.02, P = 0.087]. Median PFS with SG and TPC was 4.2 months and 3.6 months, respectively (HR 0.86, 95% CI 0.72-1.03); ORR (95% CI) was 23% (18% to 27%) and 14% (10% to 18%). The most common grade ≥3 treatment-related adverse event (TRAE) with SG was neutropenia (35%, including 12% with febrile neutropenia). Incidence of grade ≥3 TRAEs (67% versus 35%) and grade 5 treatment-emergent adverse events (TEAEs; 7% versus 2%) was higher with SG versus TPC. In the SG group, 16/25 grade 5 TEAEs were infections with neutropenia mostly occurring early in the treatment course of patients with multiple risk factors for febrile neutropenia. Primary prophylactic granulocyte colony-stimulating factor (G-CSF) usage with SG and TPC was 21% and 22%, respectively.

Conclusions

SG did not result in a significant improvement in OS or PFS compared with TPC in pretreated aUC, although SG activity was demonstrated by a higher ORR. Early toxicity-related complications with SG may have impacted efficacy outcomes.

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来源期刊

Annals of Oncology 医学-肿瘤学

CiteScore

63.90

自引率

1.00%

发文量

3712

审稿时长

2-3 weeks

期刊介绍： Annals of Oncology, the official journal of the European Society for Medical Oncology and the Japanese Society of Medical Oncology, offers rapid and efficient peer-reviewed publications on innovative cancer treatments and translational research in oncology and precision medicine. The journal primarily focuses on areas such as systemic anticancer therapy, with a specific emphasis on molecular targeted agents and new immune therapies. We also welcome randomized trials, including negative results, as well as top-level guidelines. Additionally, we encourage submissions in emerging fields that are crucial to personalized medicine, such as molecular pathology, bioinformatics, modern statistics, and biotechnologies. Manuscripts related to radiotherapy, surgery, and pediatrics will be considered if they demonstrate a clear interaction with any of the aforementioned fields or if they present groundbreaking findings. Our international editorial board comprises renowned experts who are leaders in their respective fields. Through Annals of Oncology, we strive to provide the most effective communication on the dynamic and ever-evolving global oncology landscape.