Low-grade (LG) upper tract urothelial carcinoma (UTUC) is a rare cancer, typically diagnosed in older patients with pre-existing kidney dysfunction. Radical nephroureterectomy is often utilized despite a low risk of progression and guidelines recommending kidney-sparing procedures for patients with LG, low-volume disease. Treatment with endoscopic ablation is associated with high rates of disease recurrence, necessitating frequent procedures. UGN-101 is a reverse thermal gel containing mitomycin (4 mg/mL) that is instilled into the renal pelvis as a viscous liquid and converts to gel at body temperature thereby optimizing drug exposure at the target area for 4-6 hours. We previously reported the response rate to treatment (Lancet Oncol 2020), leading to FDA approval of UGN-101 (JELMYTO® [mitomycin] for pyelocalyceal solution), and now report final results of a Phase 3 open-label, single-arm, multicenter trial that evaluated the efficacy, durability, and safety of UGN-101 for primary, non-surgical, chemoablative treatment of LG UTUC.
Patients with biopsy-proven, LG UTUC were enrolled to receive 6 weekly instillations of UGN-101 (maximum volume 15cc) via retrograde catheter to the renal pelvis and calyces. All patients had measurable tumor 5-15mm diameter above the ureteropelvic junction. Patients with bilateral disease or ureteral tumors were eligible if those areas were treated prior to enrollment. The primary endpoint was complete response as assessed by ureteroscopy, wash cytology, and for-cause biopsy at the primary disease evaluation (PDE) visit performed 4-6 weeks following the last instillation. A complete response (CR) was defined as negative ureteroscopic evaluation, negative cytology, and, if warranted, negative biopsy. Patients achieving CR were intended to continue monthly maintenance treatments for up to 11 months, with quarterly ureteroscopic assessments. Durability of response at 12 months was a key secondary endpoint. Safety was assessed through adverse event monitoring.
Of 74 patients enrolled, 71 received at least one dose of UGN-101 (intent-to-treat population). Fifty-eight percent (41/71) achieved CR at PDE. Maintenance regimens varied from 0-11 doses, with a median of 6 in the 71% (29/41) receiving at least one dose. At 12-months, CR was maintained in 23/31 (74.2%) evaluable patients, and in 23/41 (56%) with CR at PDE. The probability a patient would remain disease-free at 12 months was estimated at 81.8% by Kaplan-Meier analysis. Median time to recurrence was not reached. Maintenance treatment did not appear to affect durability of response. There were no treatment-related deaths. The most common reported adverse events were ureteric stenosis, urinary tract infection, hematuria, flank pain, nausea, dysuria, renal dysfunction, abdominal pain, and vomiting. Patients who received induction treatment only had a rate of ureteric stenosis of 29% compared with 44% in the overall population.
Final data from the OLYMPUS Trial demonstrate that non-surgical chemoablation of LG UTUC with UGN-101, a novel reverse thermal gel formulation of mitomycin, results in durable response for up to 12 months in the majority of patients who achieve CR. UGN-101 offers a kidney-sparing alternative for the treatment for LG UTUC that reduces disease recurrence and avoids the morbidity associated with radical nephroureterectomy. These data serve as a new benchmark for kidney-preserving treatment of LG UTUC.
Trial Registration Number: NCT02793128
DURABILITY OF RESPONSE TO CHEMOABLATIVE TREATMENT OF LOW-GRADE UPPER TRACT UROTHELIAL CARCINOMA WITH A MITOMYCIN-CONTAINING REVERSE THERMAL HYDROGEL: FINAL RESULTS OF THE OLYMPUS TRIAL
Bladder Cancer > Upper Tract Urothelial Carcinoma
Presented By: Surena F. Matin
Authors: Seth Lerner
Phillip M. Pierorazio
Jonathan A. Coleman
The OLYMPUS Study Group