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

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作   者：

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

作者机构：

Sheba Med Ctr;  Univ Calif Los Angeles;  Indiana Univ Sch Med;  John Wayne Canc Inst;  Weill Med Coll;  Mem Sloan Kettering Canc Ctr;  Univ Michigan;  Mayo Clin Phoenix;  Div Urol;  Dept Urol;  Univ Washington;  Ohio State Univ;  Scott Dept Urol;  Baylor Coll Med;  Univ N Carolina;  Brady Urol Inst;  Ctr Comprehens Canc;  Penns State Hlth Milton S Hershey Med Ctr;  Mayo Clin Hlth Syst;  UroGen Pharma;  Cleveland Clin;  Mayo Clin Jacksonville;  Loyola Univ Med Ctr;  Johns Hopkins Univ;  Loma Linda Univ;  Glickman Urol & Kidney Inst;  Univ Iowa;  Urol Ctr Las Vegas;  Thomas Jefferson Univ Hosp;  Univ Texas MD Anderson Canc Ctr;  Rabin Med Ctr;  Cornell Univ; 

关键词：

clinical trial;  mitomycin;  urinary bladder neoplasms; 

期刊名称：

The Journal of Urology

i s s n：

0022-5347

年卷期：

2022 年 207 卷 4 期

页   码：

779-788

页   码：

摘   要：

Purpose: Our goal was 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. Materials and Methods: In this open-label, single-arm, multicenter, phase 3 trial (NCT02793128), patients >= 18 years of age with primary or recurrent biopsy-proven low-grade upper tract urothelial carcinoma 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 followup; 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.