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

Powles T, Tagawa S, Vulsteke C, Gross-Goupil M, Park SH, Necchi A, De Santis M, Duran I, Morales-Barrera R, Guo J, Sternberg CN, Bellmunt J, Goebell P, Kovalenko M, Boateng F, Sierecki M, Wang L, Sima CS, Waldes J, Loriot Y, Grivas P (2025)

Publication Type: Journal article

Publication year: 2025

Journal

Annals of Oncology Elsevier

DOI: 10.1016/j.annonc.2025.01.011

Abstract

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.

Authors with CRIS profile

Peter Goebell Urologische Klinik

Involved external institutions

Cardiovascular Research Foundation US United States (USA) (US) Harvard University US United States (USA) (US) Gilead Sciences, Inc. US United States (USA) (US) Institut Gustave-Roussy FR France (FR) University of Washington US United States (USA) (US) Queen Mary University of London GB United Kingdom (GB) AZ Maria Middelares BE Belgium (BE) Centre Hospitalier Universitaire de Bordeaux / CHU Bordeaux FR France (FR) Sungkyunkwan University (SKKU) KR Korea, Republic of (KR) Università Vita-Salute San Raffaele (UniSR) IT Italy (IT) Charité - Universitätsmedizin Berlin DE Germany (DE) Marqués de Valdecilla University Hospital / Hospital Universitario de Marqués de Valdecilla (HUMV) ES Spain (ES) Vall d'Hebron University Hospital / Hospital Universitari Vall d'Hebron ES Spain (ES) Beijing Cancer Hospital CN China (CN)

How to cite

APA:

Powles, T., Tagawa, S., Vulsteke, C., Gross-Goupil, M., Park, S.H., Necchi, A.,... Grivas, P. (2025). Sacituzumab govitecan in advanced urothelial carcinoma: TROPiCS-04, a phase III randomized trial. Annals of Oncology. https://doi.org/10.1016/j.annonc.2025.01.011

MLA:

Powles, T., et al. "Sacituzumab govitecan in advanced urothelial carcinoma: TROPiCS-04, a phase III randomized trial." Annals of Oncology (2025).

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