LBA-16\u2003NEPHRON-SPARING MANAGEMENT OF LOW GRADE (LG) UTUC WITH UGN-101 (MITOMYCIN GEL) FOR INSTILLATION: THE OLYMPUS TRIAL EXPERIENCE

Abstract

INTRODUCTION AND OBJECTIVES: Only 30% of UTUC patients receive endoscopic, nephron-sparing treatments due to (1) high grade histology, (2) tumor burden, or (3) unfavorable tumor location. Endoscopically unresectable LG UTUC is routinely managed by nephroureterectomy (NU) predisposing patients to renal insufficiency and the risk of requiring hemodialysis. In this trial, patients received endocavitary therapy using a novel reverse thermal hydrogel containing mitomycin (UGN-101). We report the results of the primary disease evaluation within 6 weeks of completing treatment of patients enrolled with endoscopically unresectable tumors. METHODS: 71 patients with biopsy proven, LG-UTUC received 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 at the time of treatment initiation (minimum lesion size >0.5 cm). Four to six weeks following the last instillation, all patients underwent a primary disease evaluation (PDE) including ureteroscopy and wash cytology. A complete response (CR) was defined as negative ureteroscopic evaluation and negative cytology. RESULTS: Forty-one of 68 patients for whom PDE data are currently available (41/68;60%) achieved a CR after induction therapy and are currently in follow-up. Of the 68 patients, 33 (48.5%) were initially characterized by the treating physician as having endoscopically unresectable tumor at baseline and 19 (58%) achieved a CR at the PDE. Overall, only 3 of 41 patients who achieved a CR have relapsed (1 at 3 months following PDE, and 2 at 9 months); 2 of these patients were considered unresectable prior to UGN-101 treatment. No treatment or disease-related deaths have occurred in the trial to date. The most common adverse events seen in the trial were urinary tract infection, ureteral narrowing and stricture formation. CONCLUSIONS: Data from the Olympus Trial suggest that a minimally invasive chemoablation approach utilizing UGN-101 in this population results in a high rate of initial disease eradication obviating the need for kidney removal in nearly half of treated individuals. Follow-up to ascertain the durability of CR in this population is ongoing. UGN-101 is an investigational new drug and, if approved by FDA, may provide an alternative for the initial management of patients with LG UTUC, including those with endoscopically unresectable disease. Source of Funding: Urogen Pharma, Ltd., 499 Park Avenue, Suite 1200, New York, NY 10022