(UroToday.com) The AUA 2021 virtual annual meeting included a late-breaking abstract session with a presentation by Dr. Karim Chamie discussing long-term recurrence free survival following UGN-101 treatment for low-grade upper tract urothelial carcinoma.
Standard treatment for low-grade upper tract urothelial carcinoma involving the renal pelvis and calyces is radical nephroureterectomy, or nephron-sparing endoscopic surgery in patients with small, unifocal tumors. Despite kidney-sparing benefits, endoscopic management of upper tract urothelial carcinoma has limitations with an overall recurrence rate of 65%, including 78% for low-intermediate grade tumors. The OLYMPUS trial (NCT02793128) previously reported an estimated durability of response of 84% at 12 months in patients achieving complete response after induction treatment with UGN-101 (JELMYTO),1 a mitomycin-containing reverse thermal gel. At today’s late-breaking abstract session at the AUA, Dr. Chamie and colleagues presented results of further long-term durability data obtained via post-approval follow-up of participants in the OLYMPUS trial.
In OLYMPUS, 71 patients were enrolled and treated with >=1 instillation of UGN-101. Of these, 42 (59%) achieved complete response at the primary disease evaluation that occurred 4-6 weeks following completion of induction therapy. At 12 months follow up 23 patients had durable complete response and the median duration of response was not estimable. Updates on disease status for the 23 patients with durable complete response were collected biannually (data cutoff March 4, 2021) following study completion. The study design for the OLYMPUS trial is as follows:
Duration of response data were available for 15 of the 23 patients who had durable complete response. Of the remaining 8 patients, 5 participated at sites that had not yet initiated the follow-up protocol, 2 had no new data available since the last assessment in OLYMPUS, and 1 was lost to follow-up. The median (range) duration of response among the 15 available patients was 28.1 months (14.6 to 37.1 months). Duration of response was calculated as the time from the first documented complete response until disease recurrence or death or last adequate disease assessment (for patients with ongoing complete response). As of the data cutoff date, 12 (80%) patients had an ongoing complete response, 2 (13.3%) patients had recurrence of low-grade upper tract urothelial carcinoma in the ipsilateral side as treated, and 1 (6.7%) patient underwent radical nephroureterectomy:
Both patients with disease recurrence underwent endoscopic ablation. Notably, radical nephroureterectomy was performed due to left ureteral stricture and there was no evidence of upper tract urothelial carcinoma at the time of surgery. No patients had progression to high-grade upper tract urothelial carcinoma or developed metastasis. Disease-specific survival was 100% at last follow-up.
Dr. Chamie concluded his updated analysis of the OLYMPUS trial with the following take-home messages:
- Long-term follow up suggests treatment with UGN-101 for low-grade upper tract urothelial carcinoma can result in a lengthy period of durable response and may exceed that achieved by surgical nephron-sparing approaches such as laser ablation (42% recurrence after a median follow up of 32 months)
- UGN-101 offers a kidney-sparing treatment alternative for patients with low-grade upper tract urothelial carcinoma
- Limitations of this study include small sample size and missing data on 8/23 patients with durable response at 12 months post-PDE visit
Presented by: Karim Chamie, MD, MSHS, Associate Professor of Urology, UCLA, Los Angeles, CA
Co-Authors: Nir Kleinmann, Phillip Pierorazio, Jay Raman, Scott Hubosky, Ahmad Shabsigh, Brian Hu, Hristos Kaimakliotis, Marcelino Rivera, Douglas Scherr, Alon Weizer, Raymond Pak, Mark Schoenberg, Elyse Seltzer
Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia, @zklaassen_md on Twitter during the 2021 American Urological Association, (AUA) Annual Meeting, Fri, Sep 10, 2021 – Mon, Sep 13, 2021.
- Kleinmann N, Matin SF, Pierorazio PM, et al. Primary chemoablation of low-grade upper tract urothelial carcinoma using UGN-101, a mitomycin-containing reverse thermal gel (OLYMPUS): An open-label, single-arm, phase 3 trial. Lancet Oncol 2020 Jun;21(6):776-785.