A phase III randomized trial of eribulin (E) with gemcitabine (G) vs standard of care (SOC) for patients (pts) with metastatic urothelial carcinoma (mUC) refractory to or ineligible for PD/PDL1 antibody (Ab): SWOG S1937 updated design.

Abstract

TPS4617 Background: UC is 2nd most common genitourinary cancer. Enfortumab vedotin (EV) + pembrolizumab became a SOC in 2023 in frontline mUC setting. In previously treated mUC setting, erdafitinib is approved for pts with FGFR alterations, while all pts have the option of sacituzumab govitecan (SG) with objective response rate (ORR) of 27% (N=113). A phase I/II CTEP study of eribulin (E) for mUC established the activity of E with ORR of 37.5% and a median progression free survival (PFS) of 4.1 months (mo) and median overall survival (OS) of 9.5 mo (N=150). A phase II CTEP study of gemcitabine-eribulin (GE) in cisplatin ineligible mUC showed ORR of 50%, median OS of 11.9 mo and median PFS of 5.3 mo (N=24). The most common Grade 3-4 toxicities included: neutropenia 63%, anemia and fatigue 29%. Pts with liver metastases benefited from therapy with 71% ORR (n=7) for GE vs 24% for E (n=49). This trial has now been amended to account for first-line treatment changes and to include SG as a control arm option. Methods: This is an updated phase III, randomized trial comparing GE vs. SOC (SG, docetaxel, paclitaxel, or G monotherapy). E is given at 1.4mg/m2 on day (D) 1 and 8 of a 21 D cycle and G is given at 1000 mg/m2 on D1 and D8. SOC follows approved dosing. There is no limit to the number/sequence of prior regimens. In brief, all pts must have: received systemic therapy with EV; received PD1/PDL1 Ab or be deemed ineligible for PD1/PDL1 Ab. The study seeks to find at least a 50% increase in the primary endpoint of OS (Hazard Ratio (HR) = 0.667). The secondary endpoints include ORR, and progression free survival (PFS). One-sided 0.05 type I error to account and 80% power to detect a 50% improvement in OS. We require 92 eligible pts in each arm for a total of 184. The amended and restructured study was approved in January of 2024. Funding: National Institutes of Health/National Cancer Institute grants U10CA180888, U10CA180819. Eribulin is provided by Eisai. Clinical trial information: NCT04579224 .