Tumor-ablative chemotherapy for low-grade upper tract urothelial carcinoma (UTUC) using a mitomycin gel formulation approved earlier this year results in a high rate of durable complete response without significant safety issues, according to a urologist who spoke about the treatment at an industry symposium during the Large Urology Group Practice Association’s 2020 virtual annual meeting.
Marketed as Jelmyto by UroGen Pharma, Inc., which sponsored the session, the treatment is indicated for use as primary treatment in adults with low-grade UTUC and as maintenance treatment for patients who have a complete response. Mitomycin gel is indicated for pyelocalyceal use only. The dose is fixed at 4 mg/mL. The medication is delivered into the ureter or kidney as a chilled liquid that within a few minutes becomes a gel as it warms to body temperature, explained Sandip Prasad, MD, MPhil, of Garden State Urology and Director of Genitourinary Surgical Oncology at Morristown Medical Center/Atlantic Health System. Each treatment takes about 5 minutes, he said. The gel fills and conforms to the renal pelvis and remains a gel for 4 to 6 hours for sustained exposure to tumor-ablative chemotherapy. It is excreted by normal urine flow.
Mitomycin gel is given once weekly for 6 weeks. Patients are assessed for response at 4 to 6 weeks by ureteroscopy. Maintenance therapy is given once a month for 11 additional instillations.
Dr Prasad reviewed data from OLYMPUS (Optimized Delivery of Mitomycin for Primary UTUC Study), the phase 3 trial upon which FDA approval in April 2020 was based. The trial included 71 patients with low-grade UTUC with tumors 5 to 15 mm in diameter. Of these, 41 (58%) had a complete response (negative ureteroscopic evaluation, negative cytology, and no for-cause biopsy) 4 to 6 weeks after up to 6 weekly instillations. The estimated durability of response at 12 months following complete response was 84%.
“Very importantly,” Dr Prasad told attendees, “the durability of response, in my opinion, is excellent. That 84% durability of response at 12 months really suggests that these tumors are completely eradicated.”
The most important adverse reaction to mitomycin gel was ureteric obstruction, which developed in 41 (58%) of 71 patients. Most ureteric obstruction cases were mild to moderate. Of the 41 patients, 36 required ureteral stent placement. The median duration of an in-dwelling stent was 51 days. The median time to first onset of ureteric obstruction was 2.4 months (range 15 to 462 days).
Disclosure: UroGen Pharma, Inc., which markets Jelmyto, sponsored the session during which Sandip Prasad, MD, MPhil, discussed the medication.