Responders to UGN-101 Have Positive RFS in Upper Tract Urothelial Cancer

Adam S. Feldman, MD, MPH

Patients who received UGN-101 induction to treat upper tract urothelial cancer (UTUC) showed high rates of recurrence-free survival (RFS) in a broader patient population than previously investigated, according to data collected from 15 centers presented at the 2024 American Urology Association Annual Meeting.¹

Among 136 cases of UTUC treated with UGN-101, the 3-year rate of RFS was 68%. The outcomes did not significantly differ based on size, location, and multifocality of disease, method of administration, or depending on chemoablative or adjuvant treatment intent.

“UGN-101 treatment demonstrates favorable recurrence-free survival rates for patients with low-grade upper tract urothelial carcinoma who respond to initial induction,” said Adam S. Feldman, MD, MPH, director of research for the department of urology at Massachusetts General Hospital, in his presentation of these data.

UGN-101, a mitomycin-containing reverse thermal gel, was approved for use based on the open-label, single-arm phase 3 OLYMPUS trial (NCT02793128), as a non-surgical kidney-sparing treatment for UTUC. In this trial, 58% of patients had a complete response and half had no evidence of disease at 12 months.² However, the enrollment criteria and trial design do not always match the real-world usage of UGN-101 following this trial due to the needs to patients with limited alternative options.

In the OLYMPUS trial, patients received chemoablation of pelvicalyceal low-grade tumors of less than 1.5 cm. The inclusion criteria in the real-world analysis included a wider range of patients such as those treated with chemoablative intent for larger tumors, those treated with adjuvant intent, ureteral tumors and multifocal with renal pelvis and ureter.

It also included those with high-grade disease in imperative indications, meaning nephroureterectomy was not a viable option due to being ineligible for surgery, having a single kidney or bilateral UTUC, or renal insufficiency.² In addition to the longitudinal data that showed durability,³ the goal of this analysis was to explore recurrence after complete response to identify factors associated with recurrence.

There were 136 renal units with UTUC in 132 patients treated, and median follow-up was 22 months (IQR, 12-27). Of these renal units, 118 were treated for low grade non-invasive disease and 100 renal units had endoscopic evaluation following induction therapy. Prior to UGN-101 induction, 59.3% had visually complete endoscopic ablation and were treated with adjuvant intent, and 40.7% had known residual disease and were treated with chemoablative intent. Multifocal disease was present in 44.4% of cases. The renal pelvis/calyces in 61.1%, ureter in 14.8%, and both in 24.1%.1 The instillation technique was retrograde in the operating department in 16.7%, retrograde in clinic in 33.3%, and ante-retrograde in 50%; in comparison, instillation of UGN-101 was retrograde in the OLYMPUS trial.

RFS was calculated only for patients who had no evidence of recurrence following UGN-101 induction (54 renal units which were endoscopically clear after induction). When stratified by chemoablative vs adjuvant intent, there was no clear difference in RFS (P = .597). Similarly, there was no clear difference when stratified by tumor size before induction of less than 1 cm, 1 to 3 cm, or greater than 3 cm (P = .419). For location, whether in the renal pelvis, ureter, or both, there was also no difference in RFS (P = .455). Antegrade or retrograde instillation also showed no difference in RFS (P = .569). Multifocality was also not associated with worse RFS outcomes.

“The numbers are small, but…there's no clear difference in RFS by tumor size, multifocality…[or] location…,” said Feldman. “What this indicates, and we've seen, is that renal pelvis, calyceal, and ureteral tumors can respond, and…even with a stent in place, there is [also a] response.”

These outcomes show that despite differences in treatment usage and patients with comorbidities, UGN-101 can be effective in preventing or delaying recurrence in those patients who were initially disease free.

REFERENCES:

1. Feldman AS, Woldu SL, Johnson B, et al. Exploring recurrence after initial response to UGN-101 induction in expanded settings. J Urol. 2024;211(5S):e891. doi:10.1097/01.JU.0001008568.76803.f1.12

2. 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

3. 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