Multinational phase 3 trial of sacituzumab govitecan in advanced urothelial carcinoma

Sacituzumab govitecan (SG), a Trop-2-directed antibody-drug conjugate, demonstrated efficacy and manageable toxicity in the phase 2 TROPHY-U-01 study in pretreated advanced urothelial carcinoma (aUC). The multinational phase 3 TROPICS-04 study compared SG versus treatment of physician’s choice (TPC; paclitaxel, docetaxel, or vinflunine) for pretreated aUC. Overall, 711 patients were randomized. After a median follow-up of 9.2 months, the primary endpoint of overall survival was not met (median OS with SG versus TPC: 10.3 months versus 9.0 months; HR 0.86; p=0.087). Median progression-free survival with SG versus TPC was 4.2 months versus 3.6 months (HR 0.86; 95% CI 0.72-1.03); the objective response rate was 23% (18-27) versus 14% (10-18). Incidence of grade ≥ 3 treatment-related adverse events (67% versus 35%) and of grade 5 treatment-emergent adverse events (7% versus 2%) was higher with SG versus TPC. The authors conclude that SG did not result ia a significant improvement in OS or PFS compared with TPC in pretreated aUC, although SG activity was demonstrated by a higher ORR.