A phase III randomized trial of eribulin (E) with or without gemcitabine versus standard of care (SOC) for metastatic urothelial carcinoma (UC) refractory to or ineligible for PD/PDL1 antibody (Ab): SWOG S1937.

Sarmad Sadeghi University of Southern California Norris Comprehensive Cancer Center, Los Angeles, CA info_outline Sarmad Sadeghi, Melissa Plets, Primo "Lucky" N. Lara, Catherine Tangen, Rick Bangs, Seth P. Lerner, Thomas W. Flaig, Daniel P. Petrylak, Ian Thompson

Authors Sarmad Sadeghi University of Southern California Norris Comprehensive Cancer Center, Los Angeles, CA info_outline Sarmad Sadeghi, Melissa Plets, Primo "Lucky" N. Lara, Catherine Tangen, Rick Bangs, Seth P. Lerner, Thomas W. Flaig, Daniel P. Petrylak, Ian Thompson Organizations University of Southern California Norris Comprehensive Cancer Center, Los Angeles, CA, SWOG Statistics and Data Management Center, Seattle, WA, University of California, Sacramento, CA, Fred Hutchinson Cancer Research Center, Seattle, WA, Bladder Cancer Advocacy Network, Bethesda, MD, Baylor College of Medicine, Houston, TX, University of Colorado Cancer Center, Aurora, CO, Yale Cancer Center, New Haven, CT, Christus Health, San Antonio, TX Abstract Disclosures Research Funding Other Background: UC is 2nd most common genitourinary cancer. Current SOC offers platinum-based (PB) first line chemotherapy (chemo) with ddMVAC or gemcitabine-cisplatin (GC) regimens. For cisplatin ineligible patients (pts), SOC includes gemcitabine-carboplatin (GCa), and in select pts pembrolizumab. Erdafitinib is approved for pts with FGFR alterations and Enfortumab vedotin (EV) is approved for previously treated pts. A phase I/II CTEP study of eribulin (E) for metastatic UC (mUC) established the activity of E in UC with objective response rate (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 an 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 5 responders in 7 pts for GE vs 12 out 49 E. Methods: This is a phase III, randomized 3 arm study comparing E vs. GE vs. SOC (docetaxel, paclitaxel, or gemcitabine). E is given at 1.4mg/m2 on day (D) 1 and 8 of a 21 D cycle. In the GE arm, gemcitabine is added to E at 1000 mg/m2 dose to D1 and D8. SOC follows standard dosing of the agents. There is no limit to the number/sequence of prior regimens. A simplified summary of eligibility criteria is presented here. All pts must have: received frontline systemic treatment such as PB chemo or a non-platinum regimen. received PD1/PDL1 Ab or be deemed ineligible for PD1/PDL1 Ab. received EV. Assuming a median OS for the SOC arm of 7 mo the study seeks to find at least a 50% increase in median OS to 10.5 mo (Hazard Ratio (HR) = 0.667). One-sided 0.0125 type I error to account for testing of two primary hypotheses (Each arm vs. SOC). 87% power to detect a 3.5 mo improvement in OS. We require 140 eligible (155 total) pts in each arm for a total of 465. The study was activated in Feb 2021 and accrual is ongoing. Clinical trial information: NCT04579224.