TY - JOUR
T1 - Sacituzumab govitecan in advanced urothelial carcinoma
T2 - TROPiCS-04, a phase III randomized trial
AU - Powles, T.
AU - Tagawa, S.
AU - Vulsteke, C.
AU - Gross-Goupil, M.
AU - Park, S. H.
AU - Necchi, A.
AU - De Santis, M.
AU - Duran, I.
AU - Morales-Barrera, R.
AU - Guo, J.
AU - Sternberg, C. N.
AU - Bellmunt, J.
AU - Goebell, P. J.
AU - Kovalenko, M.
AU - Boateng, F.
AU - Sierecki, M.
AU - Wang, L.
AU - Sima, C. S.
AU - Waldes, J.
AU - Loriot, Y.
AU - Grivas, P.
N1 - Publisher Copyright:
© 2025
PY - 2025/1/1
Y1 - 2025/1/1
N2 - 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.
AB - 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.
KW - SN-38
KW - antibody–drug conjugate
KW - bladder cancer
KW - metastatic urothelial carcinoma
KW - sacituzumab govitecan
KW - topoisomerase I inhibitor
UR - http://www.scopus.com/inward/record.url?scp=86000366411&partnerID=8YFLogxK
U2 - 10.1016/j.annonc.2025.01.011
DO - 10.1016/j.annonc.2025.01.011
M3 - Article
C2 - 39934055
AN - SCOPUS:86000366411
SN - 0923-7534
VL - 36
SP - 561
EP - 571
JO - Annals of Oncology
JF - Annals of Oncology
IS - 5
ER -