Nonsurgical primary chemoablation with the mitomycin-containing reverse thermal gel UGN-102 showed promise as an alternative to repetitive surgery for patients with low-grade non–muscle invasive bladder cancer (NMIBC), according to findings from the phase 2b OPTIMA II trial published in the Journal of Urology.1
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%. An estimated 73% of these patients with CRs maintained their response 12 months after starting therapy. The median duration of response had not been reached.
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.
Explaining the rationale for evaluating UGN in this population, the authors wrote, “Studies of aqueous preparations of mitomycin suggest that chemoablation with mitomycin may obviate the need for surgery in some patients or reduce the perioperative morbidity associated with surgery secondary to lower volume disease, and may be associated with fewer clinically significant adverse effects.”
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. In this group, 39 patients remained disease-free at 6 months following the start of treatment, 30 were disease-free 9 months after, and 12 were disease-free 12 months after.
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.
1. 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