In the single-arm phase III OLYMPUS trial reported in The Lancet Oncology, Kleinmann et al found that primary chemoablation of low-grade upper tract urothelial carcinoma using a mitomycin-containing reverse thermal gel (UGN-101) resulted in disease eradication in more than half of patients.

As noted by the investigators, most patients with low-grade upper tract urothelial cancer are treated with radical nephroureterectomy.

Study Details

In the trial, conducted at sites in the United States and Israel between April 2017 and November 2018, 71 patients with primary or recurrent disease measuring 5 to 15 mm in maximum diameter were to receive six once-weekly instillations of UGN-101. Instillations consisting of mitomycin gel (4 mg/mL) were dosed according to volume of the renal pelvis and calyces to a maximum of 60 mg/instillation and were administered via retrograde catheter to the renal pelvis and calyces.

Complete response was defined as a negative 3-month ureteroscopic evaluation, negative cytology, and negative for-cause biopsy. A complete response rate of 15% was the performance goal of the trial.

Complete Response Rate

Overall, 61 patients completed all six instillations. Complete response was observed in 42 patients (59%; P < .0001 vs 15% target), including 36 (59%) of those receiving six instillations and 6 (60%) of 10 receiving less than six instillations.

Among 41 patients with complete response entering the follow-up period, 6 (15%) had recurrence during the median follow-up period of 11.0 months. The estimated durability of response at 12 months was 84.2%, and the estimated median time to recurrence was 13.0 months.

Adverse Events

The most common adverse events of any grade were ureteric stenosis (44%), urinary tract infection (32%), hematuria (31%), flank pain (30%), and nausea (24%). Grade ≥ 3 adverse events occurred in 42% of patients, with the most common being ureteric stenosis (8%) and hydronephrosis (6%).

Drug- or procedure-related serious adverse events occurred in 27% of patients, including ureteric stenosis, hydronephrosis, flank pain, urosepsis, and chronic obstructive pulmonary disease. Adverse events led to death in three patients, due to cerebrovascular accident, failure to thrive, and unknown cause, respectively; none of the deaths was considered related to treatment.

The investigators concluded, “Primary chemoablation of low-grade upper tract urothelial cancer with intracavitary UGN-101 results in clinically significant disease eradication and might offer a kidney-sparing treatment alternative for these patients.”

Seth P. Lerner, MD, of the Department of Urology, Baylor College of Medicine, is the corresponding author for The Lancet Oncology article.

Disclosure: The study was funded by UroGen Pharma. For full disclosures of the study authors, visit thelancet.com.