UTUC agent linked to high rate of disease eradication

An investigational mitomycin formulation for the non-surgical treatment of low-grade upper tract urothelial cancer (LG-UTUC) is continuing to show promise. The latest data from the OLYMPUS Trial suggest that a minimally invasive chemoablation approach utilizing UGN-101, a novel reverse thermal hydrogel containing mitomycin, may result in a high rate of initial disease eradication, possibly obviating the need for kidney removal in select patients.

The findings, which were presented at the AUA annual meeting in Chicago, showed that 41 out of 68 patients (60%) for whom primary disease evaluation (PDE) data were available achieved a complete response after induction therapy. The authors found that 33 of the patients (48.5%) were initially characterized by the treating physician as having endoscopically unresectable tumor at baseline, and 19 patients (58%) achieved a complete response at the PDE.

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“I believe UGN-101 has the potential to improve quality of life and lower morbidity by helping some patients avoid nephroureterectomy. Renal pelvis cancer typically presents in an elderly patient population with innately reduced kidney function, and UGN-101 would be an alternative to the potential morbidity of a major surgery, as well as the downstream deleterious effects from kidney removal,” said study investigator John L. Gore, MD, of the University of Washington in Seattle.

In the current analysis, only three of 41 patients who achieved a complete response had relapsed. One patient relapsed at 3 months following PDE, and two patients relapsed at 9 months. UGN-101 is designed to enable longer exposure of mitomycin to urinary tract tissue, and it is delivered using standard ureteral catheters. Currently, only 30% of UTUC patients receive endoscopic, nephron-sparing treatments.

The standard of care for endoscopically unresectable LG-UTUC is nephroureterectomy. However, this predisposes patients to renal insufficiency and increases the risk of requiring hemodialysis.

Next:Treatment well tolerated“UGN-101 appeared to be associated with complete chemoablation in 60% of patients. It was well tolerated, with most treatment-related adverse events characterized as mild or moderate and transient. The common side effects included ureteral narrowing, ureteral stricture, hydronephrosis, urinary tract infection, flank pain, and creatinine elevation,” Dr. Gore told Urology Times.

He said urologists are limited by the current options available for treating UTUC. The endoscopic options are inadequate and available instillational adjuncts lack the needed dwell time to have benefit.

“The repeated procedures also risk injury to the upper urinary tract, and patients are prone to a high recurrence rate. The other alternative is nephroureterectomy, which is overkill for many low-grade upper tract cancers. UGN-101 was devised to address this unmet need and has the potential to change practice for patients with low-grade renal pelvis cancer,” said Dr. Gore.

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As part of this international trial, 71 patients with biopsy-proven LG-UTUC received six weekly instillations via retrograde catheter of UGN-101 (maximum volume, 15 cc; concentration of 4 mg mitomycin/mL) to the renal pelvis and calyces. All the patients had measurable tumor at the time of treatment (minimum lesion size, >0.5 cm), and following the last instillation (4 to 6 weeks), each patient underwent a PDE including ureteroscopy and wash cytology. The authors defined a complete response as negative ureteroscopic evaluation and negative cytology.

The company developing this product (UroGen Pharma Ltd.) intends to seek regulatory approval of UGN-101 in LG-UTUC based on data from all 71 patients. It initiated its rolling submission of the New Drug Application to the FDA in December 2018.

“This is a very positive update,” Mark P. Schoenberg, MD, chief medical officer of UroGen, toldUrology Times. He said it is possible that approval could occur within the next 12 months.

Adam S. Feldman, MD, MPH, of Massachusetts General Hospital and Harvard Medical School, Boston, said this is an exciting trial for a host of reasons and urologists were anxiously awaiting the latest trial update.

“We are all very excited about it,” said Dr. Feldman, who was not involved in the study. “Our instrumentation is quite small and limited in the volume of tumor we can treat endoscopically, so this product offers us an ability to treat a tumor that would otherwise be untreatable endoscopically.”

UroGen Pharma funded the study.