(UroToday.com) Dr. Surena Matin presented the final results of the OLYMPUS trial, Optimized DeLivery of Mitomycin for Primary UTUC Study (Olympus) at the Best of Bladder Cancer poster session.
In this single-arm phase III trial, patients with primary low-grade upper tract urothelial carcinoma underwent 6 once-weekly instillations of UGN-101 (JELMYTO), a reverse-thermosensitive polymer gel containing 4mg/mL of mitomycin, followed by once-monthly maintenance instillations for up to 11 months in complete responders. Patients were required to have <15mm of tumor at the initiation of treatment (either by having low volume disease to begin with or through debulking).
The initial results of the OLYMPUS trial were published in Lancet Oncology in April 2020.1 This demonstrated a complete response in 47/72 patients (59%) on ureteroscopic evaluation 4-6 weeks after completion of induction therapy. The complete response (CR) rate was similar (20/34 or 58.8%) among patients with unresectable tumors at baseline. 86% of patients completed the induction therapy. 37% of patients had at least one grade 3 adverse event including 6 with grade 3 ureteric stenosis.
In this highlighted poster presentation, Dr. Matin presented the key secondary endpoint of durability of response. 29/41 complete responders received at least one maintenance dose, with a median of 6 doses among these 29 patients. At 12 months, 23/31 patients (74.2%) had a persistent complete response. (This was 81.8% estimated 1-year persistent CR by Kaplan-Meier analysis, which would imply a ~48% 12 month CR rate overall.) No difference in durability of response was noted between patients who did and did not receive maintenance therapy. There was a 44% rate of ureteric stenosis in the overall population, although this was only 29% among patients who received induction therapy only, suggesting that the risks of maintenance therapy might outweigh the benefits.
During the question and answer session, Dr. Matin discussed the significant ongoing interest among urologists in using UGN-101 as a single-dose immediately after ureteroscopic complete resection similar to the way mitomycin is used in the bladder. He expects this to be evaluated in the near future, potentially using lower doses than were used in this trial.
The other major issue addressed in the question and answer session was the concern for ureteral stricture, since 31 patients (43%) experienced ureteral stenosis and 11/71 (15%) of patients in the initial report were left with long-term indwelling nephroureteral stents. Dr. Matin himself now administers UGN-101 through a percutaneous nephrostomy tube, which dramatically simplifies the logistics of administration and may decrease the risk of ureteral stricture by eliminating the need for ureteral manipulation. Treatment holiday or steroid administration in addition to the omission of maintenance therapy was also suggested by the study investigators as a way to decrease this risk.
Presented by: Surena F. Matin, MD, Monteleone Family Foundation Distinguished Professor, University of Texas MD Anderson Cancer Center
Written by: Marshall Strother, MD, Society for Urologic Oncology Fellow, Division of Urologic Oncology, Fox Chase Cancer Center, Philadelphia PA @mcstroth during the 2020 Society of Urologic Oncology Annual Meeting – December 2-5, 2020 – Washington, DC
References:
1. Kleinmann N, Matin SF, Pierorazio PM, et al. Primary chemoablation of low-grade upper tract urothelial carcinoma using UGN-101, a mitomycin-containing reverse thermal gel (Olympus): an open-label, single-arm, phase 3 trial. The Lancet Oncology. 2020;21(6):776-785.
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