PD18-07 PRIMARY CHEMOABLATION FOR THE TREATMENT OF LOW GRADE UPPER TRACT UROTHELIAL CARCINOMA: THE OLYMPUS TRIAL

Abstract

INTRODUCTION AND OBJECTIVE: Low grade (LG) upper tract urothelial cancer (UTUC) accounts for 40% of all UTUC diagnosed in the US. Although LG UTUC has a low risk of progression, radical nephroureterectomy (RNU) is the standard of care. Endoscopic ablation is used in only 20% of patients and is associated with a high rate of local recurrence. UGN-101 is a locally applied, reverse thermal gel containing mitomycin that allows for sustained exposure and increased dwell time. We report results of a Phase 3 open label, single arm, multicenter trial which evaluated the efficacy and safety of UGN-101 as primary, non-surgical chemoablative treatment of LG UTUC. METHODS: 74 patients with biopsy-proven, LG UTUC were enrolled to receive 6 weekly instillations via retrograde catheter of UGN-101 (maximum volume 15cc; concentration of 4 mg mitomycin/ ml) to the renal pelvis and calyces. All patients had measurable tumor 5-15mm diameter. Four to six weeks following the last instillation, eligible patients underwent a primary disease evaluation (PDE) including ureteroscopy and wash cytology, and biopsy of any suspicious lesions. A complete response (CR) was defined as negative ureteroscopic evaluation and negative cytology. Patients achieving CR were to continue to monthly maintenance and quarterly follow up for durability. RESULTS: Of 74 patients enrolled, 71 received at least one dose of UGN-101 (ITT population). Fifty-nine percent (42/71) achieved a CR. Thirty-four (34/71;48%) were characterized by the treating physician as having endoscopically unresectable tumor at baseline and 59% (20/34) of these individuals also achieved a CR. Durability of CR was estimated at 89% at six months and 84% at 12 months by Kaplan-Meier analysis. Median time to recurrence was 13 months. Overall, 7 of 41 patients who achieved a CR have had a documented recurrence. No treatment-related deaths occurred to date. The most common reported adverse events were ureteral stricture, urinary tract infection, hematuria, flank pain and nausea. CONCLUSIONS: Data from the OLYMPUS Trial demonstrate that non-surgical chemoablation of LG UTUC with intracavitary UGN- 101 results in a high rate of initial disease eradication that is durable in the majority of patients. UGN-101 potentially meets an unmet medical need and, may provide an alternative to repetitive endoscopic surgery or nephroureterectomy for patients with LG UTUC.