However, endoscopic management, as with the bladder, is limited to some degree by the high recurrence rates and the requirement for repeated procedures for surveillance. Similar stage disease in the bladder is often treated with intravesical therapy to help reduce the risk of recurrence – mitomycin-C is the most common agent for low-grade disease of the bladder, though recent data suggests gemcitabine might be an equivalent option. Unfortunately, no such agents are approved for UTUC and dwell time limits their utility. As such, any agent that has efficacy in reducing recurrences with increased dwell time would have a significant impact on the management of this disease process.
One of the most exciting options in this space has been UGN-101 (MITOGEL-TM), a prolonged release, reverse thermal gel formulation containing mitomycin. Developed in Israel, this gel is administered via retrograde catheter to a maximum volume of 15cc (volume determined by careful measurement of renal pelvic volumes under fluoroscopic control). Once instilled, due to patient body heat, it solidifies allowing prolonged contact of the mitomycin to the urothelium. Then, it eventually degrades and passes. The formulation is 4 mg MMC per 1 mL of gel.
Lerner briefly reviewed the compassionate use (non-randomized patient trial) results – promising enough to proceed to this first clinical trial. 44% CR rates noted.
In this study, the first to assess Mitogel, 33 patients with biopsy-proven, unilateral LG-UTUC were enrolled and treated with 6 weekly instillations. All patients had measurable tumor at the time of treatment initiation (minimum lesion size >0.5 cm) – inclusion criteria were: tumor between 0.5-1.5 cm (can have received partial treatment to get tumors to this size), biopsy confirmed low-grade disease (and cytology to rule out high-grade), and tumor located superior to UPJ. They excluded patients with CIS, high-grade disease within 2 years, and current systemic therapy.
Thirty-four percent of enrolled patients had tumors located in regions of the kidney not amenable to surgical resection. Patients were primarily male, mean age 70.7, 27% had unreachable tumors at baseline, and 56% had multiple tumors at baseline.
At follow-up, 4-6 weeks following the last instillation, patients underwent a primary disease evaluation (PDE) including ureteroscopy of the treated system and wash cytology. A complete response (CR) was defined as negative ureteroscopic evaluation and negative wash cytology.
- CR patients may receive monthly instillations as maintenance.
- Plan is for q3month ureteroscopy and evaluation
In this interim analysis report, of the 34 patients, 33 have undergone PDE assessments. The complete response rate in the intent to treat (ITT) cohort is 58.8% (20/34). On subsequent cystoscopies, this appeared to be a durable CR. Beyond that, partial response was also evident – 5/34 (14.7%).
Treatment-emergent adverse events included urinary tract infection, flank pain, and transient creatinine elevation with most reported as mild or moderate.
- 40% had “ureteral” complications – hydronephrosis, stricture, stenosis, obstruction, and narrowing – per Lerner, all but 2 have resolved
This was glossed over, but I think represents the greatest concern
In this population with low-grade disease, 40% ureteral complications is concerning
- 40% also had flank pain
- >30% had renal events, LUTS, nausea/vomiting
As mentioned, this is an interim analysis. All participating subjects will be followed for a minimum of 12 months following PDE to determine the durability of disease control. More importantly, the study continues to enroll patients, with top-line data expected later this year.
This is very exciting data and we look forward to final results. However, the complication rate appears a bit high and needs further granularity and clarification.
Presented by: Seth Lerner, MD, FACS, Baylor College of Medicine
Co-Authors: Nir Kleinmann, Ramat Gan, Israel, Phillip Pierorazio, Baltimore, MD, Surena Matin, Houston, TX, Joshua Stern, Bronx, NY, Michael Woods, Chapel Hill, NC, Christopher Weight, Minneapolis, MN, Scott Hubosky, Philadelphia, PA, Guilherme Godoy, Houston, TX, Brian Hu, Loma Linda, CA, Mitchell Humphreys, Phoenix, AZ, Jennifer Linehan, Santa Monica, CA, Hristos Kaimakliotis, Indianapolis, IN, Alon Weizer, Ann Arbor, MI, Ahmad Shabsigh, Columbus, OH, Douglas Scherr, New York, NY, Ifat Klein, Gil Hakim, Ra'anana, Israel, Angela Smith, Chapel Hill, NC, Mark Schoenberg, Bronx, NY
Written by: Thenappan Chandrasekar, MD, Clinical Fellow, University of Toronto, @tchandra_uromd at the 2018 AUA Annual Meeting - May 18 - 21, 2018 – San Francisco, CA USA