Efficacy and Safety of Sacituzumab Govitecan in Cisplatin-Ineligible Patients with Metastatic Urothelial Cancer After Immunotherapy - Expert Commentary
The TROPHY-U-01 trial is a multicohort, open-label phase II study to evaluate efficacy and safety of SG and SG combination treatments in patients with mUC. In a recent publication, Petrylak et al. reported the findings from the second cohort of 38 cisplatin-ineligible patients with disease progression after ICI treatment.
The median follow-up was 9.3 months. The median age was 73 years, 61% of patients were male, and 82% of patients were White. Visceral metastasis was present in 66% of patients. Most patients (74%) had received two or more previous cancer treatments, with all patients receiving previous ICI treatment. During the trial, patients received a median of six cycles and 11.5 doses of SG, with a median treatment duration of 4.4 months. At data cutoff, 95% of patients had discontinued SG, among whom 53% had experienced disease progression. The objective response rate (ORR) was 32% (95% CI, 17.5 – 48.7). Target lesions were smaller in 22 of 32 patients, with the rest of the patients remaining unassessed. The median time to response was 1.4 months (95% CI, 1.3 – 1.5). The median duration of response was 5.6 months (95% CI, 2.8 – 13.3). Median progression-free survival was 5.6 months (95% CI, 4.1 – 8.3) and the median overall survival was 13.5 months (95% CI, 7.6 – 15.6).
All patients experienced one or more treatment-emergent AE (TEAE) and 87% had grade 3 or higher events. The most common TEAEs were diarrhea (66%), nausea (53%), fatigue (50%), alopecia (50%), and neutropenia (45%). The most common grade 3 or higher TEAEs include neutropenia (34%), anemia (24%), leukopenia (19%), fatigue (18%), diarrhea (16%), febrile neutropenia (8%), and colitis (8%). TEAEs led to treatment interruption in 61% of patients, dose reduction in 37%, and subsequent discontinuation in 21% of patients.
Due to the limited treatment options available to patients with mUC who experience progression on ICI treatment and are ineligible for cisplatin-based chemotherapy, SG carries potential in this population. Given the changing treatment landscape with enfortumab vedotin-pembrolizumab combination as the first-line treatment, the role of SG in second line will need to be defined further.
Written by: Bishoy M. Faltas, MD, Director of Bladder Cancer Research, Englander Institute for Precision Medicine, Weill Cornell Medicine
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