UGN-101 Shows Promise for Upper Tract Urothelial Cancer Durability

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.

REFERENCES:

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. https://bit.ly/3liG6jn

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