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

Abstract

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.

Keywords: clinical trial; mitomycin; urinary bladder neoplasms.

Graphical abstract

Figure 1.

Patient flow diagram, modified from Kleinmann et al to show final disposition of patients at the April 30, 2020 final data cutoff. a, more than 1 reason could be given. b, patient traveled out of the country.

Figure 2.

Kaplan-Meier analysis for durability in 41 patients with complete response at PDE during maintenance/followup.

Figure 3.

Swimmer plot for 41 individual patients with complete response at PDE during maintenance/followup. Among 41 patients with complete response at PDE 12 did not receive maintenance treatment, while 29 received ≥1 maintenance instillation of UGN-101. There were 8 patients with documented disease recurrence and 23 patients without disease recurrence at 12 months. Patients who did not have documented disease recurrence or who died prior to recurrence were censored at their last assessment or date of death. Asterisk indicates none of the deaths was considered related to study drug or study procedure.