JU Insight: 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

By: Surena F. Matin, MD; Phillip M. Pierorazio, MD; Nir Kleinmann, MD; John L. Gore, MD; Ahmad Shabsigh, MD; Brian Hu, MD; Karim Chamie, MD; Guilherme Godoy, MD; Scott G. Hubosky, MD; Marcelino Rivera, MD; Michael O'Donnell, MD; Marcus Quek, MD; Jay D. Raman, MD; John J. Knoedler, MD; Douglas Scherr, MD; Christopher Weight, MD; Alon Weizer, MD; Michael Woods, MD; Hristos Kaimakliotis, MD; Angela B. Smith, MD; Jennifer Linehan, MD; Jonathan Coleman, MD; Mitchell R. Humphreys, MD; Raymond Pak, MD; David Lifshitz, MD; Michael Verni, MD; Ifat Klein, MD; Marina Konorty, PhD; Dalit Strauss-Ayali, PhD; Elyse Seltzer, MD; Mark Schoenberg, MD; Seth P. Lerner, MD | Posted on: 01 Apr 2022

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 2021; https://doi.org/10.1097/JU.0000000000002350.

Study Need and Importance

Kidney-sparing treatment options such as endoscopic ablation are recommended for patients with low-grade upper tract urothelial carcinoma (UTUC) whose tumors are small and favorably located. Endoscopic management, however, is associated with a high rate of local disease recurrence. We previously reported interim results from a phase 3 trial in which clinically significant disease eradication was observed following 6 weekly induction instillations of UGN-101 (a mitomycin-containing reverse thermal gel), irrespective of whether the patients’ tumors were resectable at baseline. We now have followed all patients with complete response to induction therapy for at least 12 months to evaluate durability of response.

Table. Proportion of 41 patients with durable complete response at followup

Time Since Primary Disease Evaluation (mos)	No. Pts with Evaluation at Followup Visit	No. Pts Maintaining Complete Response (%)
3	38	35 (85)
6	38	33 (80)
9	35	28 (68)
12	31	23 (56)
Percentage is calculated from no. of patients with complete response at primary disease evaluation visit (41).

What We Found

Of 41 patients who had complete response to induction therapy with UGN-101, 23 (56%) remained in complete response after 12 months (see table). Use of monthly maintenance treatment with UGN-101 varied widely with 12 patients receiving no maintenance treatment and 29 patients receiving ≥1 maintenance instillation (median 6, range 1–11). There was no clear association between durability of response and maintenance treatment with 6/12 patients (50%) and 17/29 patients (59%) maintaining complete response; however, an increasing number of instillations of UGN-101 appeared to be associated with increased incidence of urinary adverse events.

Limitations

The primary limitations of this study are the small sample size, reflecting the rarity of low-grade UTUC, and its open-label, single-arm design, which does not permit direct comparison of the observed recurrence rate with rates of local disease recurrence in patients managed endoscopically.

Interpretations for Patient Care

Primary chemoablation with UGN-101 is a nonsurgical, kidney-sparing treatment that results in clinically significant and durable disease eradication, thereby providing an additional option for the management of patients with low-grade UTUC, including those with multifocal disease and those whose tumors are difficult to treat endoscopically.