Retrospective, observational analysis of real-world safety outcomes in sacituzumab govitecan (SG)-treated patients (pts) with locally advanced/metastatic urothelial cancer (la/mUC).

709 Background: In the rapidly evolving la/mUC treatment landscape, new therapies need to be integrated into management of pts. SG, a Trop-2–directed antibody drug conjugate, showed improved overall survival and manageable safety in pts with la/mUC who progressed on platinum-based chemotherapy and immune checkpoint inhibitor therapy in TROPHY-U-01 (NCT03547973). Safety of SG was previously reported in a retrospective cohort study using US Flatiron Health electronic health record–derived de-identified database of pts ≥ 18 yrs with la/mUC initiating SG from Dec 2019 - Oct 2022. We now present results from the expansion cohort with an additional year of follow-up. Methods: Pts in the expansion cohort had initiated SG from Dec 2019 - Jul 2023. Data on treatment (tx) patterns, abstracted adverse events (AEs) of interest (AEs chosen a priori based on what was observed in clinical studies), tx discontinuation, hospitalization, and granulocyte colony-stimulating factor (G-CSF) use were summarized using descriptive statistics. Results: Of 220 SG-treated pts (male, 73%; median age, 66 yrs), most (63%) received enfortumab vedotin (EV) monotherapy in the prior tx line. The most common AEs of interest were diarrhea (n = 110 [50%]), neutropenia (n = 77 [35%]), and nausea (n = 76 [35%]). Febrile neutropenia and infections secondary to neutropenia occurred in 18 (8%) and 9 (4%) pts, respectively (Table). Of the 220 pts, 141 (64%) had a documented reason for SG discontinuation; 106 (75%) pts discontinued due to disease progression and 19 (13%) due to AEs/toxicities. Of these latter 19 pts, 3 each (16%) discontinued due to neutropenia and fatigue. Discontinuation rate based on prespecified AEs of interest occurring during therapy was 3% (n = 7). Of the 220 pts, 62 (28%) were hospitalized due to AEs. During SG tx, 104 (47%) pts received G-CSF at any time; 64 (29%) received G-CSF primary prophylaxis. Of 79 pts with neutropenia onset during SG index line, 14 (18%) received G-CSF primary prophylaxis, 29 (37%) received secondary prophylaxis and 36 (46%) received G-CSF treatment. Conclusions: This is the largest analysis to date of SG use in a real-world population with la/mUC, with a significant number of EV-pretreated patients. Although AEs such as diarrhea, neutropenia, and nausea occurred frequently, tx discontinuation rate (based on prespecified AEs) was low. Observed AEs were consistent with the known safety profile of SG. Incident AEs of interest, n (%); (N = 220). Anemia 36 (16) Neutropenia 77 (35) Febrile neutropenia | Infections secondary to neutropenia a 18 (8) | 9 (4) Sepsis 25 (11) UTI 34 (15) Diarrhea 110 (50) Nausea | Vomiting 76 (35) | 41 (19) Stomatitis 21 (10) Fatigue 52 (24) Infusion-related reaction 1 (<1) a Prevalent numbers are reported since baseline status was not abstracted for these events.