UGN-102 effective in patients with low-grade NMIBC

Findings from the phase 2b OPTIMA II trial published in the Journal of Urology showed that nonsurgical primary chemoablation with the mitomycin-containing reverse thermal gel UGN-102 may be an alternative to repetitive surgery for patients with low-grade non–muscle invasive bladder cancer (NMIBC).^1,2

The study specifically focused on patients with intermediate-risk NMIBC. At 3-months after treatment initiation, the complete response (CR) rate with UGN-102 in these patients was 65%. Using Kaplan-Meier analysis, the researchers estimated that the probability of maintaining a durable response 9 months after achieving a CR (12 months after starting treatment) was 73%.

“The significant treatment response and sustained durability observed in this trial indicate that UGN-102 has the potential to become a nonsurgical alternative for these chronically relapsing patients, who typically undergo repetitive surgeries,” William C. Huang, M.D., FACS, professor of Urology and Radiology and Vice Chair of Urology at NYU Langone Health and principal investigator of the OPTIMA II trial, stated in a press release. “Even more encouraging is that 12 months after treatment was initiated, approximately 73% achieved durable response.”

Transurethral resection of bladder tumors (TURBT) is the standard of care for patients with low-grade, intermediate NMIBC. However, recurrence is common in these patients, requiring repeated TURBT, which is associated with several risks, including failure to cure, bladder perforation, bleeding that necessitates a hospital stay, and repeated anesthesia in older patients that is linked to cognitive decline.

In the multicenter prospective, open-label, single-arm OPTIMA II trial (NCT03558503), 63 patients with biopsy-proven, low-grade, intermediate-risk NMIBC were treated with up to 6 once-weekly UGN-102 instillations. The median age was 63 years (range, 33-96) and there were 38 males and 25 females. Twenty-seven patients were aged <65 years, 11 were aged 65 to <75 years, and 25 were aged ≥75 years. Most (n = 55) patients were Caucasian.

Overall, 72.1% of patients had tumors ≤3 cm, 98.4% had noninvasive papillary sarcoma, and 98.4% had low-grade papillary urothelial carcinoma. Prior low-grade NMIBC episodes occurred in 77.8% of patients and 44.4% had a low-grade NMIBC episode ≤1 year of their current diagnosis. The median number of prior TURBTs in recurrent patients was 3 (range, 0-13), including 37 and 28 patients who had received ≥2 and ≥3 prior TURBTs, respectively.

All 63 patients received at least 1 UGN-102 instillation and 57 (90%) patients received all 6 UGN-102 instillations. The primary end point of the study was CR, which the trial design defined as, “The proportion of patients with negative endoscopic examination, negative cytology, and negative for-cause biopsy 3 months after treatment initiation.” The investigators conducted a quarterly follow-up of the complete responders for up to 1 year to evaluate the durability UGN-102’s impact.

Overall, 41 of the 63 patients achieved a CR at the 3-month follow-up from the start of treatment. In this group, 39 (95%) patients remained disease-free at 6 months following the start of treatment (3 months after achieving CR), 30 (73%) were disease-free 9 months after starting treatment, and 25 (61%) were disease-free 12 months after starting treatment.

The majority of adverse events (AEs) were considered to be mild to moderate. Overall, 63% (n = 40) of patients had treatment-emergent AEs (TEAEs) that investigators categorized as related to UGN-102 itself or procedure. All-grade TEAEs occurring in ≥10% of patients included dysuria, urinary frequency, hematuria, micturition urgency, urinary tract infection, and fatigue. There were no serious TEAEs related to the study treatment or procedure.

Based on the positive outcomes in this study, the ongoing global, randomized, open-label, phase 3 ATLAS trial (NCT04688931) is comparing UGN-102 with or without TURBT versus TURBT alone in patients with low-grade, intermediate-risk NMIBC.

References

1. The Journal of Urology Publishes Results of UroGen Pharma’s Phase 2b Study of UGN-102 in Patients with Low-Grade Intermediate Risk Non-Muscle Invasive Bladder Cancer (LG IR-NMIBC). Published online October 5, 2021. Accessed October 5, 2021. https://bit.ly/3D91krg.

2. Chevli KK, Shore ND, Trainer A, Smith AB, et al. Primary chemoablation of low-grade intermediate-risk non-muscle-invasive bladder cancer using ugn-102, a mitomycin-containing reverse thermal gel (OPTIMA II): A phase 2b, open-label, single-arm trial. [published online ahead of print August 26, 2021. J Urol. doi: 10.1097/JU.0000000000002186