UGN-101 Shows Promise for Upper Tract Urothelial Cancer Durability


Maintenance UGN-101 therapy demonstrated good durability of response in initial responders with low-grade upper tract urothelial cancer, as evidenced by a low rate of disease progression in a multicenter, longitudinal follow-up study.

Yair Lotan, MD

Yair Lotan, MD

A low rate of disease progression was observed among initial responders with upper tract urothelial cancer (UTUC) who received maintenance UGN-101 (mitomycin gel; Jelmyto) therapy, indicating good durability of response, according to longitudinal follow-up of a multicenter study presented at the 2024 American Urological Association (AUA) Annual Meeting.1

Treatment with UGN-101 previously led to favorable rates of recurrence-free survival (RFS) in patients with low-grade, noninvasive (LGTa) UTUC. However, its effectiveness in high-grade disease remains unclear due to limited data.2

This analysis is limited due to small numbers of patients with high-grade disease and raises concerns about the potential for high recurrence and progression rates in this higher-risk group.1

“The goal of our collaboration was to look retrospectively at real-world data. In the real world, we find significant differences from the OLYMPUS trial [NCT02793128],” explained Yair Lotan, MD, of UT Southwestern Medical Center, during the meeting. “There are larger tumors than 1.5 centimeters, there was complete ablation followed by adjuvant use, about a third of patients had ureteral tumors, which were not part of the study, and it also included some patients with high-grade disease…so it offers an opportunity to get some insight that wasn't possible just with a strict clinical trial.”

UGN-101 is a novel delivery system for intracavitary treatment of UTUC. In 2020, the FDA approved UGN-101 for small volume residual low-grade UTUC based on findings from the phase 3 OLYMPUS trial.3

In this study presented at AUA 2024, investigators assessed a large multicenter cohort of patients treated with UGN-101 using the longest follow-up available. Data from 15 centers on patients treated with UGN-101 for UTUC were collected.

A total of 136 cases of patients with UTUC treated with UGN101 were included and had a cumulative median (IQR) follow-up of 22 months (range, 12-27). This included 107 cases of LGTa UTUC.

Patients were mostly male (70%), mostly White (83%), and 78% of patients had a history of smoking. Nine percent of patients had ureteral-only involvement, most had recurred following prior intracavitary treatment, and 50% had multifocal disease.

“In the OLYMPUS trial, all of the treatments were retrograde, but in this, half the patients had antegrade treatment with [percutaneous nephrostomy (PCN)], 43% of patients had complete ablation prior to UGN installation, so this was adjuvant, and as mentioned, 9% were high-grade,” said Lotan.

RFS was determined only in patients who achieved complete response (CR) after UGN-101 induction. All patients treated with UGN-101 had progression-free survival calculated for, and disease progression was defined as: 1) grade progression from low-grade to high-grade disease, 2) stage progression, or 3) development of metastatic disease.2

In the presentation, Lotan shared that very good response rates were observed among patients with absence of visible disease with complete ablation (n = 36; 69.2%) and tumors <1 cm (n = 7; 70%).1 For tumors between 1-3 cm, the response rate was 33.3% (n = 11), and for those >3 cm, the response rate was 23.5% (n = 4).1

In the original cohort of the study, 54 had a CR. Only 13 patients of the 54 received maintenance and none of them recurred.

“We had 54 patients who had a CR in this initial dataset, and with a median follow-up of 2 years, we found that 68% [had no evidence of disease (NED)]. So it was quite reassuring from a standpoint that these patients who had a response maintained the response,” added Lotan.

Only 1 patient of the 54 developed progression of disease. Subsequent nephroureterectomy showed high-grade pT3N0 disease.

Overall, maintenance UGN-101 was associated with overall good durability of response in initial responders, and there was a low rate of progression observed.

“We need a larger cohort and more data at the big benefit of maintenance therapy. Remember, if patients don't want to have a PCN tube for a year and get monthly treatments, they also don't necessarily want to go to the operating room every month, so this is going to be a challenge. We have a prospective registry that hopefully will be able to elucidate not only efficacy but also long-term toxicity, which is a little harder to get on retrospective cohorts,” added Lotan.

Background on UGN-101 and the OLYMPUS Trial

The multicenter, open-label, single-arm, phase 3, OLYMPUS study evaluated the safety, tolerability, and tumor ablative effect of the UGN-101 in patients with low-grade UTUC.4 The primary end point of the study was CR based on ureteroscopy and cytology following a 6-week induction course of UGN-101.

Findings showed a CR rate of 59% in patients with at least 1 dose of the thermal gel at the time of the primary disease evaluation visit, which was 4 to 6 weeks following the initial therapy.4

Long-term follow-up data of the OLYMPUS trial showed that the mitomycin-containing reverse thermal gel, UGN-101, led to a median durability of response of 28.9 months (range, 14.6-47.6 months) in adult patients with low-grade UTUC. At the data cutoff, data were available for 16 patients, 13 of whom remained in CR, and 2 who had recurrence of low-grade UTUC. One patient underwent radical nephroureterectomy to ureteral stricture without evidence of UTUC at the time of surgery. Additionally, no patients progressed to high-grade disease.

1. Longitudinal follow up of multicenter study of UGN-101 for upper tract urothelial cancer. Presented at: 2024 American Urological Association Annual Meeting. May 3-6, 2024, San Antonio, Texas. PD41-11
2. Woldu SL, Johnson B, Murray KS, et al. Longitudinal follow up of multicenter study of UGN-101 for upper tract urothelial cancer. J Urol. 2024;211(5S):e890. doi:10.1097/01.JU.0001008568.76803.f1.11
3. FDA approves first therapy for treatment of low-grade upper tract urothelial cancer. News release. FDA. April 15, 2020. Accessed May 3, 2024.
4. Matin SF, Pierorazio PM, Kleinmann N, et al. 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. J Urol. 2022;207(4):779-788. doi:10.1097/JU.0000000000002350
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