On April 15, 2020, the FDA approved the alkylating drug mitomycin gel (Jelmyto; UroGen Pharma) for the treatment of patients with low-grade upper-tract urothelial cancer. Mitomycin is a combination of chemotherapy and a sterile hydrogel that stops the transcription of DNA into RNA and halts the synthesis of protein, thereby blocking the ability of cancer cells to multiply. The FDA granted mitomycin gel priority review, breakthrough therapy, fast track, and orphan drug designations.
“This is the first approval specifically for patients with low-grade UTUC [upper-tract urothelial cancer] and provides an option for some patients who may otherwise require a nephroureterectomy,” said Richard Pazdur, MD, Director of the FDA’s Oncology Center of Excellence.
The FDA approval of mitomycin gel was based on results of the open-label, single-arm, phase 3 clinical trial known as OLYMPUS. The study included 71 patients with upper-tract urothelial cancer. All patients were either treatment-naïve or had recurrent low-grade upper-tract urothelial cancer with at least 1 measurable papillary tumor. The patients received mitomycin gel once weekly for 6 weeks; in patients who achieved a complete response, the treatment was given on a monthly basis for up to 11 additional months.
The primary end point was complete response after 3 months of therapy. Of the 71 patients in the trial, 41 (58%) had a complete response after 6 months of weekly treatments and 19 (46%) continued to have a complete response after the 12-month mark.
The most common (≥20%) adverse events were ureteric obstruction, flank pain, urinary tract infection, hematuria, renal dysfunction, fatigue, nausea, abdominal pain, dysuria, and vomiting. Serious adverse reactions, which included ureteric obstruction, flank pain, and urosepsis, occurred in 37% of patients. Of the patients with ureteric obstruction that resulted from treatment with mitomycin gel, 51% had obstruction that persisted or did not resolve completely.