Primary chemoablation with UGN-102, an investigational mitomycin-containing reverse thermal gel, has demonstrated encouraging trial results as a possible treatment for low-grade intermediate-risk nonmuscle-invasive bladder cancer (LG IR-NMIBC), according to study findings presented during the AUA2021 Virtual Experience.

“We believe that patients will be receptive to this new nonsurgical treatment option, as there is currently nothing else like this approved as a primary treatment therapy,” principal investigator William C. Huang, MD, professor of urology and radiology and vice chair of urology at NYU Langone Health in New York, New York, said in an interview. “UGN-102 has the potential to be the first, non-surgical primary therapeutic treatment for patients suffering from LG IR-NMIBC, providing an alternative to repetitive surgery.”

The results are from the phase 2b open-label OPTIMA II trial, which included 63 patients treated with UGN-102. They received 6 once-weekly instillations of UGN-102 in an office setting. Of these, 41 (65%) achieved a complete response (CR) at 3 months. In this group, 39 (95%), 30 (73%), and 25 (61%) remained disease-free at 6, 9, and 12 months, respectively, after treatment initiation. The 9-month duration of response rate (the probability that a patient will maintain a CR for at least 9 months [12 months after treatment initiation]) was 73%, the investigators reported.

Dr Huang and colleagues defined CR as negative endoscopic examination, negative cytology, and negative for-cause biopsy 3 months after treatment initiation.

The medication was generally well tolerated. Adverse events were primarily mild or moderate, with the most common being dysuria (41% of patients), pollakiuria (21%), hematuria (16%), urinary urgency (14%), urinary tract infection (14%), and fatigue (11%).

Dr Huang said major challenges exist in the current standard of care for LG IR-NMIBC, as it is a disease associated with high recurrence rates (historically up to 80%) and multi-focality (increased disease burden) that requires multiple repeated transurethral resection of bladder tumor (TURBT) procedures.

He pointed out that management of patients with low-risk and high-risk NMIBC appears clear, but the optimal treatment for those with intermediate-risk disease is uncertain because they make up a more heterogeneous group of patients.

“It is also worth noting that unlike surgery, which focuses on the removal of visible lesions, chemoablation with UGN-102 provides treatment for the entire field of urothelium exposed to the drug,” Dr Huang said. “Since we know that IR-NMIBC is often multi-focal and that microscopic disease is often present that eludes detection using standard endoscopic techniques, we may find that chemoablation is a particularly valuable strategy for managing patients with this form of bladder cancer.”

It is estimated that LG IR-NMIBC represents approximately 25% of newly diagnosed bladder cancer cases in the US, Dr Huang said. “These patients are chronically relapsing and currently, their only treatment option is repeated TURBT with or without instillation of intravesical chemotherapy.” In fact, some patients will require repeated TURBT procedures per year, which can lead to increased morbidity (ie, surgically-related complications) along with the risks associated with repetitive anesthesia.

“Thus we believe that at this current time, patients with LG IR-NMIBC are the ideal patients for this therapy. If approved, UGN-102 would be the first, nonsurgical primary therapeutic treatment for patients suffering from LG IR-NMIBC, providing an alternative to repetitive surgery.”

UGN-102 is similar to the mitomycin-containing agent approved for the treatment of low-grade upper tract urothelial carcinoma (Jelmyto), but they are different compounds. Both agents are made by UroGen Pharma.

Disclosure: This research was supported by UroGen Pharma. Please see the original reference for a full list of disclosures.

Reference

Chevli K, Shore N, Trainer A, 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. Presented at: AUA2021 Virtual Experience held September 10-13, 2021. Abstract PD43-02.