AUA 2019: Nephron-sparing Management of Low Grade UTUC with UGN-101 for Instillation: The Olympus Trial Experience

Chicago, IL ( Low grade upper tract urothelial carcinoma (LG UTUC) can be managed with endoscopic resection/ablation however, the associated high recurrence rate requires repetitive intervention and intercavitary therapy for the frequently recurrent and multifocal disease. Many patients have difficulty to access tumors or unresectable tumor volume, requiring radical nephroureterectomy (RNU). Preliminary data from a compassionate use program demonstrated that LG UTUC could be chemically ablated with mitomycin gel (UGN-101).

The presented study design (the OLYMPUS study) is presented in figure 1. This was a single arm prospective phase 3 open-label study in patients with LG UTUC. The primary objective was to evaluate the safety and tumor ablative effect of UGN-101. All patients received six once-weekly instillations of UGN-101 with a mitomycin dosage of 4 mg/1ml of TC-3 gel. The target population was 74 patients with pathologically confirmed LG non-invasive UTUC. The trial was designed with a 90% power to demonstrate that the observed complete response rate is above 15%.

Figure 1 – OLYMPUS study design:

The inclusion criteria included new or recurrent LG UTUC with biopsy confirmed LG and cytology negative for high grade (HG) disease. Patients needed to have at least 1 papillary LG tumor (0.5-1.5 cm in diameter), and the tumor needed to be located superior to the ureteropelvic junction (UPJ). The full inclusion and exclusion criteria are shown in figure 2.

Figure 2- OLYMPUS trial inclusion and exclusion criteria:

The final cohort included 71 patients with their baseline data shown in table 1. The results demonstrated that out of the 71 patients, a complete response rate of 59% was witnessed. A total of 66% had undergone six months of surveillance, and 89% remained disease free at six months of follow-up. A total of 48% were deemed to be endoscopically unresectable, with 59% of them achieving a complete response, and 85% remaining disease free at six months of follow-up. 

Table 1 – Demographic data:

When considering the adverse events (Table 2), 2.8% had life-threatening events, and 4.2% were fatal (stroke one patient, failure to thrive one patient, and sudden death one patient). It is noteworthy that all life-threatening and fatal events were not related to UGN-101 or the procedure.

Table 2- Adverse events:

Dr. Lerner concluded by stating that data from the OLYMPUS trial suggest that UGN-101 can ablate LG tumors with a high initial complete response rate, that appears durable, with an ongoing follow-up. The high rate of initial disease eradication obviated the need for kidney removal in 48% of patients deemed to have unresectable disease. Lastly, UGN-101 is an investigational drug that if approved by the FDA, may provide an alternative for the initial management of patients with LG UTUC.

Presented by: Seth Lerner, MD, FACS, Baylor College of Medicine

Written By: Hanan Goldberg, MD, Urologic Oncology Fellow (SUO), University of Toronto, Princess Margaret Cancer Centre @GoldbergHanan at American Urological Association's 2019 Annual Meeting (AUA 2019), May 3 – 6, 2019 in Chicago, Illinois

email news signup