A phase III randomized trial of eribulin (E) with gemcitabine 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
TPS894 Background: UC is the 2nd most common genitourinary cancer. Enfortumab vedotin (EV) + pembrolizumab became a SOC in 2023 in frontline mUC setting. There is no established standard of care for the subsequent lines of therapy limiting treatment options to platinum-based chemotherapy, docetaxel, paclitaxel, or gemcitabine. Erdafitinib remains an option for pts with FGFR3 alterations. A phase I/II CTEP study of eribulin (E) for mUC established the activity of E with an objective response rate (ORR) of 37.5%, 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% each). Pts with liver metastases benefited from therapy with an ORR of 71% (n = 7) for GE vs. 24% for E (N = 49). Methods: This is an updated phase III, randomized trial comparing GE vs. SOC (docetaxel, paclitaxel, or gemcitabine monotherapy). E is given at 1.4mg/m2 on day (D) 1 and 8 of a 21 D cycle. Gemcitabine is added to E at 1000 mg/m2 on D 1 and D 8. SOC follows approved dosing. There is no limit to the number/sequence of prior regimens. Pts with bone only metastases are eligible. All pts must have: received systemic therapy with EV; received PD1/PDL1 Ab or been 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). Secondary endpoints include ORR and PFS. This design has a power of 80% and a one-sided alpha of 0.05 to detect a HR = 0.667. We require 184 pts (92 in each arm) to yield a total of 168 eligible pts. Funding: National Institutes of Health/National Cancer Institute grants U10CA180888, U10CA180819. Eribulin is provided by Eisai. Clinical trial information: NCT04579224 .
Article Details
Journal Info
Journal of Clinical Oncology
Lippincott Williams & Wilkins
Authors (19)
Sarmad Sadeghi
University of Southern California, Los Angeles, CA
Samuel Callis
SWOG Statistical Center, Fred Hutchinson Cancer Research Center, Seattle, WA
Primo N. Lara
University of California Davis Comprehensive Cancer Center Sacramento California USA
Stephanie A. Berg
Department of Medical Oncology Dana‐Farber Cancer Institute Boston Massachusetts USA
Jason Robert Brown
Division of Solid Tumor Oncology, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH
Adanma Ayanambakkam
Stephenson Cancer Center, University of Oklahoma Health Sciences, Oklahoma City, OK
Suzanne Cole
From the Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda (A.B.A., N.S., S.N., L.L., L.C.), the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore (J.H.-C.), and the Investigational Drug Branch, Cancer Therapy Evaluation Program, National Cancer Institute, National Institutes of Health, Rockville (H.S., E.S.) — all in Maryland; the Alliance Statistics and Data Management Center, Mayo Clinic, Rochester, MN (K.V.B., M.O., C.M., G.P.B.); AdventHealth Cancer Institute and the University of Central Florida, Orlando (G.S.); Dana–Farber/Harvard Cancer Center, Boston (S.B., B.M.); UNC Lineberger Comprehensive Cancer Center, Chapel Hill (W.Y.K.), and Duke University Medical Center and Duke Cancer Institute, Durham (J.H., S.H.) — both in North Carolina; the University of Kansas Cancer Center, Westwood (R.P.); Memorial Sloan Kettering Cancer Center, New York (M.Y.T., M.J.M., J.E.R.), and Roswell Park Comprehensive Cancer Center, Buffalo (G.C.) — both in...
Elizabeth R. Kessler
University of Colorado Cancer Center, Anschutz Medical Campus, Aurora, CO
Daniel A. Vaena
West Cancer Center and Research Institute, Germantown, TN
Greg R. Angstreich
USC/Norris Comprehensive Cancer Center, Irvine, CA
Theodore Stewart Gourdin
Medical University of South Carolina, Charleston, SC
Nataliya Mar
University of California Irvine, Irvine, CA
Rick Bangs
Bladder Cancer Advocacy Network Bethesda Maryland USA
Darrell Nakagawa
SWOG GU Bladder Patient Advocate, Schaumburg, IL
Siamak Daneshmand
Department of Urology, Keck School of Medicine of University of Southern California, Norris Comprehensive Cancer Center
Ian Murchie Thompson
UT Health San Antonio, San Antonio, TX
Thomas W. Flaig
University of Colorado School of Medicine, Anschutz Medical Campus, Aurora
Daniel P. Petrylak
Yale School of Medicine, New Haven, CT
Seth P. Lerner
Department of Urology, Baylor College of Medicine, Houston