Antegrade Administration of Mitomycin Gel Provides Safe, Effective Approach in Upper Tract Urothelial Carcinoma

Data from a retrospective analysis demonstrated that mitomycin gel (Jelmyto) was safe and effective when administered using an antegrade approach in real-world populations of patients with low-grade upper tract urothelial cancer, according to findings presented at the 2022 American Urological Association Annual Meeting.¹

Administration of mitomycin gel via retrograde administration using a ureteral catheter is more widely used than antegrade administration via percutaneous nephrostomy tube. For example, all evaluable patients in the pivotal OLYMPUS trial (NCT02793128) received 6 once-weekly treatments via a retrograde approach.²

Investigators noted that patients required general anesthesia for the procedure, which may correlate with an increased cost and morbidity. Additionally, repeat procedures via catheter may be a contributing factor to the development of ureteric stenosis.

Mitomycin gel was approved for either antegrade or retrograde administration in 2020 based on data from the phase 3, single-arm OLYMPUS study.³ To circumvent the associated complications with retrograde administration, investigators pooled data from multiple institutions at which patients received mitomycin gel via antegrade administration. All patients underwent induction therapy of 6 once-weekly administrations of mitomycin gel administered using percutaneous nephrostomy tube.¹

The retrospective analysis identified 26 patients who received treatment across 4 institutions. In terms of efficacy, 50% of patients had a complete response (CR) and 46% had a partial response (PR) at postinduction ureteroscopy, with 1 patient experiencing progression to invasive disease. Further, at a median follow-up of 7 months, no patients with a CR experienced disease recurrence.¹

In an analysis of the safety data, no patients reported impaired renal function during the follow-up period and 15% of patients reported ureteral stenosis. Other adverse effects included fatigue (27%), flank pain (19%), urinary tract infection (12%), sepsis (8%), and hematuria (8%). No patients died on treatment.

“[Mitomycin gel] is efficacious as a [chemoablation] agent in adult patients with low-grade upper tract urothelial cancer, and while it’s FDA approved for both antegrade and retrograde administration, prior reports are limited to the retrograde experience,” study investigator Kyle Rose, MD, a urologic oncology fellow at Moffitt Cancer Center in Tampa, Florida said in a news release.⁴ “These data provide additional evidence that instillation via a nephrostomy tube is an effective instillation method with a safety profile that offers an encouraging option to appropriate patients.”

Nine patients (35%) received at least 1 dose of maintenance therapy with mitomycin gel and 6 patients (23%) in the retrospective analysis had solitary kidneys.¹

“In addition to the lower morbidity profile, percutaneous administration allowed for chemoablation without the use of general anesthesia,” the study authors wrote, noting that larger studies are needed to conclusively identify potential advantages of antegrade vs retrograde approaches.¹

Mitomycin gel is indicated for the primary chemoablation treatment of patients with low-grade upper tract urothelial cancer. The reverse thermal gel contains 4 mg of mitomycin per mL of gel and is instilled via antegrade or retrograde administration only becoming a semisolid gel at body temperature. The gel dissolves during urine production over 4 to 6 hours, allowing for increased time at the primary tumor site.²

In a final analysis of OLYMPUS, among 71 patients in the intention-to-treat population, 59.2% had a CR and 11.3% had a PR. Emergence of high-grade disease was reported among 8.5% of patients and no response was observed in 16.9% of patients. Additionally, investigators noted that 34 patients had tumors which were deemed unresectable at baseline and 58.8% of patients in that group had a CR.²

The durability of CR at 12 months was 82% (95% CI, 66%-91%) with 56% (95% CI, 40%-72%) of patients maintaining CR at a 12-month analysis.² In terms of safety, investigators highlighted ureteric obstruction may increase in tandem with the number of doses and procedures. The most common incidence was documented as ureteric stenosis (43.7%) and was reported after a median of 6 instillations.²

Among patients with a CR, 29 went on to receive maintenance therapy for a median of 6 instillations (range, 1-11).²

References

1. Rose K, Narang G, Rosen G, et al. Antegrade administration of reverse thermal mitomycin gel for primary chemoablation of upper tract urothelial carcinoma via percutaneous nephrostomy tube: a multi-institutional real-world experience. J Urol. 2022;207(suppl 5):e1013.doi:10.1097/JU.0000000000002643.06
2. Matin SF, Pierorazio PM, Kleinmann N, et al. Durability of response to primary chemoablation of low-grade upper tract urothelial carcinoma using UGN-101, a mitomycin-containing reverse thermal gel: OLYMPUS trial final report. J Urol. 2022;207(4):779-788. doi:10.1097/JU.0000000000002350
3. FDA approves mitomycin for low-grade upper tract urothelial cancer. FDA. April 15, 2020. Accessed May 16, 2022. bit.ly/3Pp3g5Z
4. UroGen highlights new data presented at AUA that adds to the evidence supporting in-office nephrostomy tube administration of Jelmyto, the only non-surgical, kidney-sparing treatment for adults with low grade upper tract urothelial cancer. News release. UroGen Pharma Ltd. May 16, 2022. Accessed May 16, 2022. bit.ly/3MBaguV