Abstract
A phase III randomized trial of eribulin (E) with or without gemcitabine vs standard of care (SOC) for metastatic urothelial carcinoma (UC) refractory to or ineligible for PD/PDL1 antibody (Ab): SWOG S1937.
Author
Sarmad Sadeghi
University of Southern California, Los Angeles, CA
info_outline
Sarmad Sadeghi, Melissa Plets, Primo N Lara, Catherine Tangen, Rick Bangs, Seth P. Lerner, Thomas W. Flaig, Daniel P. Petrylak, Ian M Thompson
Full text
Authors
Sarmad Sadeghi
University of Southern California, Los Angeles, CA
info_outline
Sarmad Sadeghi, Melissa Plets, Primo N Lara, Catherine Tangen, Rick Bangs, Seth P. Lerner, Thomas W. Flaig, Daniel P. Petrylak, Ian M Thompson
Organizations
University of Southern California, Los Angeles, CA, SWOG Statistics and Data Management Center, Seattle, WA, University of California Davis Comprehensive Cancer Center, Sacramento, CA, Fred Hutchinson Cancer Research Center, Seattle, WA, SWOG Cancer Research Network, San Antonio, TX, Baylor College of Medicine, Houston, TX, University of Colorado Cancer Center Anschutz Medical Campus, Aurora, CO, Yale School of Medicine, New Haven, CT, UT Health San Antonio, San Antonio, TX
Abstract Disclosures
Research Funding
U.S. National Institutes of Health
U.S. National Institutes of Health
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.
Clinical status
Clinical
1 clinical trial
8 organizations
16 drugs
12 targets
Clinical trial
A Phase III Randomized Trial of Eribulin (NSC #707389) With Gemcitabine Versus Standard of Care (Physician's Choice) for Treatment of Metastatic Urothelial Carcinoma Refractory to, or Ineligible for, Anti PD1/PDL1 TherapyStatus: Recruiting, Estimated PCD: 2027-08-15
Organization
Fred Hutchinson Cancer Research CenterOrganization
SWOG Cancer Research NetworkOrganization
Baylor College of MedicineOrganization
Yale School of MedicineOrganization
UT Health San Antonio, MD Anderson Cancer CenterDrug
ddMVACDrug
GCSFDrug
GCaDrug
pembrolizumabDrug
erdafitinibDrug
EVDrug
eribulinDrug
GemcitabineDrug
docetaxelDrug
TiragolumabDrug
FF-10832Target
GCaTarget
carboplatinTarget
Nectin-4Target
ddMVACTarget
FGFRaTarget
eribulinTarget
cisplatinTarget
GemcitabineTarget
microtubules