Durability of Response to Primary Chemoablation of Low-Grade Upper Tract Urothelial Carcinoma Using UGN-101, a Mitomycin-Containing Reverse Thermal Gel: OLYMPUS Trial Final Report.

Purpose: To evaluate long-term safety and durability of response to UGN-101, a mitomycin-containing reverse thermal gel, as primary chemoablative treatment for low-grade upper tract urothelial carcinoma (UTUC). Materials and Methods: In this open-label, single-arm, multi-center, phase 3 trial (NCT02793128), patients ≥18 years of age with primary or recurrent biopsy-proven low-grade UTUC received 6 once-weekly instillations of UGN-101 via retrograde catheter to the renal pelvis and calyces. Those with complete response (defined as negative ureteroscopic evaluation, negative cytology, and negative for-cause biopsy) 4-6 weeks after the last instillation were eligible for up to 11 monthly maintenance instillations and were followed for ≥12 months with quarterly evaluation of response durability. Durability of complete response was determined by ureteroscopic evaluation; duration of response was estimated by the Kaplan-Meier method. Treatment-emergent adverse events (TEAEs) were monitored.Results: Of 71 patients who initiated treatment, 41 (58%) had complete response to induction therapy and consented to long-term follow up; 23/41 patients (56%) remained in complete response after 12 months (95% CI: 40, 72), comprising 6/12 (50%) who did not receive any maintenance instillations and 17/29 (59%) who received ≥1 maintenance instillation. Kaplan-Meier analysis of durability was estimated as 82% (95% CI: 66, 91) at 12 months. Ureteric stenosis was the most frequently reported TEAE (31/71, 44%); an increasing number of instillations appeared to be associated with increased incidence of urinary TEAEs.Conclusions:Durability of response to UGN-101 with or without maintenance treatment is clinically meaningful, offering a kidney-sparing therapeutic alternative for patients with low-grade disease.

The Journal of urology. 2021 Dec 17 [Epub ahead of print]

Surena F Matin, Phillip M Pierorazio, Nir Kleinmann, John L Gore, Ahmad Shabsigh, Brian Hu, Karim Chamie, Guilherme Godoy, Scott G Hubosky, Marcelino Rivera, Michael O'Donnell, Marcus Quek, Jay D Raman, John J Knoedler, Douglas Scherr, Christopher Weight, Alon Weizer, Michael Woods, Hristos Kaimakliotis, Angela B Smith, Jennifer Linehan, Jonathan Coleman, Mitchell R Humphreys, Raymond Pak, David Lifshitz, Michael Verni, Ifat Klein, Marina Konorty, Dalit Strauss-Ayali, Gil Hakim, Elyse Seltzer, Mark Schoenberg, Seth P Lerner

Department of Urology, The University of Texas MD Anderson Cancer Center, Houston, TX., Brady Urological Institute, The Johns Hopkins University, Baltimore, MD., Department of Urology, Sheba Medical Center, Ramat Gan, Israel., Department of Urology, University of Washington Medical Center, Seattle, WA., Department of Urology, The Ohio State University Comprehensive Cancer Center, Columbus, OH., Department of Urology, Loma Linda University, Loma Linda, CA., Department of Urology, UCLA, Los Angeles, CA., Scott Department of Urology, Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX., Department of Urology, Sidney Kimmel Medical College at Thomas Jefferson University Hospitals, Philadelphia, PA., Department of Urology, Mayo Clinic Health System, Rochester, MN., Department of Urology, University of Iowa, Iowa City, IA., Department of Urology, Loyola University Medical Center, Maywood, IL., Division of Urology, Penn State Health Milton S. Hershey Medical Center, Hershey, PA., Department of Urology, Weill Medical College of Cornell University, New York, NY., Cleveland Clinic, Glickman Urological and Kidney Institute, Cleveland, OH., Department of Urology, University of Michigan, Ann Arbor, MI., Department of Urology, Indiana University School of Medicine, Indianapolis, IN., Department of Urology, University of North Carolina School of Medicine, Chapel Hill, NC., Department of Urology, John Wayne Cancer Institute, Santa Monica, CA., Department of Urology, Memorial Sloan-Kettering Cancer Center, New York, NY., Department of Urology, Mayo Clinic-Phoenix, Scottsdale, AZ., Department of Urology, Mayo Clinic-Jacksonville; Jacksonville, FL., Department of Urology, Rabin Medical Center, Tel Aviv, Israel., Urology Center of Las Vegas, Las Vegas, NV., UroGen Pharma, Ra'anana, Israel., UroGen Pharma, Princeton, NJ.