Sacituzumab Govitecan Fails to Significantly Improve Survival in Advanced Urothelial Carcinoma

According to final analysis results from the phase 3 TROPICS-04 trial, sacituzumab govitecan did not significantly improve survival compared to standard chemotherapy among previously treated patients with advanced urothelial carcinoma. 

“Until recently, patients with advanced urothelial carcinoma whose cancer progresses on or after platinum-based chemotherapy and programmed cell death-(ligand) 1 [PD-(L)1] inhibitors have had relatively limited approved treatment options and poor prognosis,” stated Thomas Powles, MD, MBBS, Barts Cancer Institute, London, United Kingdom, and coauthors. “Sacituzumab govitecan, an antibody directed to Trophoblast cell surface antigen 2 (Trop-2), has shown notable antitumor activity in various solid tumors.”

This study enrolled 711 patients with advanced urothelial carcinoma who experienced disease progression after treatment with platinum-based chemotherapy and checkpoint inhibitor therapy. Patients were randomized on a 1-to-1 basis to receive either 10 mg/kg of intravenous sacituzumab govitecan (n = 355) or physician’s choice paclitaxel, docetaxel, or vinflunine (n = 356). The primary end point was overall survival (OS). Key secondary end points included progression-free survival (PFS), objective response rate (ORR), and safety. 

At a median follow-up of 9.2 months, median OS was 10.3 months in the sacituzumab govitecan arm and 9 months in the physician’s choice arm (hazard ratio [HR] 0.86; 95% confidence interval [CI], 0.73 to 1.02; P = .087). Median PFS was 4.2 months in the sacituzumab govitecan arm and 3.6 months in the physician’s choice arm and the ORR was 23% and 14%, respectively. 

Grade ≥3 treatment-related adverse events occurred in 67% of patients in the sacituzumab govitecan arm and 35% of patients in the physician’s choice arm. The treatment-related adverse event most observed in the sacituzumab govitecan arm was neutropenia (35%), with 12% of patients experiencing febrile neutropenia. Treatment-related adverse events led to dose reductions in 37% of patients, dose interruptions in 52% of patients, and treatment discontinuation in 11% of patients. 

“Further validation of [sacituzumab govitecan] activity is needed in prospective randomized trials that utilize consistent primary prophylaxis with G-CSF starting at cycle 1 to mitigate the risk of complications arising from [sacituzumab govitecan]-related high-grade neutropenia,” concluded Dr Powles et al. 

Source:

Powles T, Tagawa S, Vulsteke C, et al. Sacituzumab govitecan in advanced urothelial carcinoma: TROPiCS-04, a phase III randomized trial. Ann Oncol. Published online: February 10, 2025. doi: 10.1016/j.annonc.2025.01.011