UGN-101 May Offer Kidney-Sparing Treatment For Low-Grade Upper Tract Urothelial Cancer

Author: By Lynda Williams, Senior medwireNews Reporter 

medwireNews: OLYMPUS trial findings suggest that the mitomycin-containing reverse thermal gel UGN-101 could offer a kidney-sparing chemoablation approach for patients with low-grade upper tract urothelial carcinoma. 

Intracavitary UGN-101 achieved a “complete response in a substantial proportion of patients” in the open-label phase III study and this might help patients avoid the need for radical nephroureterectomy, report Seth Lerner, from Baylor College of Medicine in Houston, Texas, USA, and co-authors in The Lancet Oncology. 

Seventy-one patients with primary or recurrent tumours measuring between 5 and 15 mm in diameter were assigned to receive six weekly instillations of UGN-101 by retrograde catheter. Each treatment contained a mitomycin dose of 4 mg/mL and was tailored to the individual patient’s renal pelvis and calyces volume, to a maximum dose of 60 mg/treatment. An 11-month course of monthly maintenance therapy was available for those who achieved a complete response to treatment. 

Overall, 59% of patients achieved a complete response at the planned primary disease evaluation 4–6 weeks after completion of treatment, defined as no disease on ureteroscopy, selective upper tract wash cytology and for-cause biopsy. 

At time of data cutoff, the patients with a complete response had been followed-up for a median of 11.0 months. Of the 20 patients who had completed their 12-month assessment, 70% continued to have a complete response and 15% had recurrence, but none had progressed to high-grade or invasive disease. 

Kaplan–Meier analysis for durability of complete response was estimated to be 84.2% at 12 months, with a median time to recurrence of 13.0 months, and further follow-up analysis is planned. 

However, the researchers note that as maintenance therapy use was “inconsistent”, they were unable to determine “the value of maintenance with respect to the durability of complete response in this cohort.” 

The most common adverse event (AE) was ureteric stenosis, occurring at grade 1–2 and grade 3 in 35% and 8% of patients, respectively, followed by urinary tract infection (30% and 3%, respectively), haematuria (28% and 3%) and flank pain (27% and 3%). AEs affecting the renal urinary system occurred in 68% of patients, with 50% of these requiring a ureteral stent. 

Treatment was discontinued because of AEs in 27% of patients, approximately half during the initial 6-week period and the remainder during maintenance therapy. There were no grade 4 or 5 treatment-related AEs. 

“These findings suggest that this alternative kidney-sparing treatment might be considered for patients with low-grade upper tract urothelial cancer, including those with multifocal disease and those who are not candidates for endoscopic ablation”, summarise Seth Lerner et al.

Writing in an accompanying comment, Robert Dreicer, from the University of Virginia in Charlottesville, USA, commends the OLYMPUS investigators on their “challenging” study, which “provides some evidence of the potential role of UGN-101 in this population with clear unmet needs.”

He notes the difficulty of performing randomised clinical trials in patients with low-grade upper tract urothelial cancer “given that the current reference standard remains endoscopic resection or radical nephroureterectomy, which makes the use of a control group highly problematic.”

Recognising the positive preliminary findings of the KEYNOTE-057 trial of pembrolizumab in a similar patient population to that of OLYMPUS, the commentator concludes that “if the updated data from [OLYMPUS] lead to regulatory approval of UGN-101, a randomised phase 2 study comparing this evolutionary advance with a potentially more revolutionary therapeutic option would be theoretically possible.” 

References 

Kleinmann N, Matin SF, Pierorazio PM, et al. Primary chemoablation of low-grade upper tract urothelial carcinoma using UGN-101, a mitomycin-containing reverse thermal gel (OLYMPUS): an open-label, single-arm, phase 3 trial. Lancet Oncol; Advance online publication 29 April 2020. doi:10.1016/S1470-2045(20)30147-9

Dreicer R. New mitomycin formulation for low-grade upper tract urothelial cancer. Lancet Oncol; Advance online publication 29 April 2020. doi:10.1016/S1470-2045(20)30159-5