SUO 2023: Primary Chemoablation for Recurrent Low Grade Intermediate Risk Non-Muscle Invasive Bladder Cancer: The ENVISION Trial

(UroToday.com) The 2023 SUO annual meeting included a late breaking abstract session on urothelial cancer, featuring a presentation by Dr. Sandip Prasad discussing results from the ENVISION trial assessing primary chemoablation for recurrent low grade intermediate risk non-muscle invasive bladder cancer. Low grade intermediate risk non-muscle invasive bladder cancer includes patients who have one or two of the following:

Presence of multiple tumors
Solitary tumor > 3 cm
Early or frequent recurrence (>=1 occurrence of low grade non-muscle invasive bladder cancer within 1 year of current diagnosis)

Patients with low grade intermediate risk non-muscle invasive bladder cancer commonly experience recurrence and are treated with repetitive TURBT, usually under general anesthesia. Repetitive TURBTs are associated with postoperative and long-term morbidity and an increased mortality risk. While clinical practice guidelines recommend adjuvant chemotherapy post-TURBT to potentially attenuate recurrence, compliance with this approach is low (10%-20%). Furthermore, there are no approved primary non-surgical treatment options in low grade intermediate risk non-muscle invasive bladder cancer.

The objective of the phase 3 pivotal ENVISION trial is to evaluate the efficacy and safety of UGN-102 as primary chemoablative therapy in patients with recurrent low grade intermediate risk non-muscle invasive bladder cancer. This is a prospective, single arm open label trial (no maintenance therapy) with the following trial schema: ENVISION trial primary chemoablation flow
UGN-102 is a mitomycin-containing reverse thermal gel, which has previously shown safety and efficacy in a phase 2b single-arm (OPTIMA II) trial¹ and a phase 3 randomized control (ATLAS) trial²in patients with newly diagnosed or recurrent low grade intermediate risk non-muscle invasive bladder cancer. The reverse thermal gel technology is important, given that it adheres to the bladder wall even after voiding, unlike regular intravesical administration of mitomycin which is excreted with urination: RT gel illustration
The primary outcome of ENVISION was complete response rate defined as the proportion of patients who achieved complete clinical response at the 3 month primary outcome assessment. Secondary outcomes included:

Duration of response up to 63 months
Durable complete response rate
Disease free survival

The safety analysis assessed incidence of treatment emergent adverse events, serious events, treatment emergent adverse events of special interest, and abnormal clinical laboratory results.

Among 240 patients in the trial that received UGN-102, the median age was 70.0 years of age (range: 30-92), 61.3% were male, and 98.6% were white. The complete baseline demographics are as follows: ENVISION trial primary chemoablation characteristics
At the complete response primary endpoint assessment at 3 months, the complete response rate was 79.2% (95% CI 73.5 – 84.1). Among the 50 patients (20.8%) that did not have a complete response, 35/50 patients had residual disease (14% overall), with only 6/50 patients (2.5% overall) having progression to high-grade disease: ENVISION trial primary chemoablation complete response
UGN-102 was generally well tolerated with 52.8% of patients having a treatment emergent adverse event. The most common mild/moderate adverse events were dysuria and hematuria. There were two serious adverse treatment related adverse events including one patient with urethral stenosis and one patient with urinary retention. There were two deaths in the cohort, both of which (pneumonia and cardiac arrest) were deemed to be unrelated to treatment: ENVISION trial primary chemoablation adverse events
Dr. Prasad concluded his presentation discussing the first results from the ENVISION trial assessing primary chemoablation for recurrent low grade intermediate risk non-muscle invasive bladder cancer with the following take-home points:

The phase 3 ENVISION trial is currently ongoing
79% of patients achieved a complete response at 3 months of follow-up
Adverse events were mostly mild to moderate in nature
Additional data evaluating the secondary endpoint of duration of response from ENVISION is anticipated in 2024
If approved, UGN-102 would be the first, non-surgical treatment option for patients with low grade intermediate non-muscle invasive bladder cancer

Presented by: Sandip M. Prasad, MD, Garden State Urology, Whippany, NJ

Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Associate Professor of Urology, Georgia Cancer Center, Wellstar MCG Health, @zklaassen_md on Twitter during the 2023 Society of Urologic Oncology (SUO) Annual Meeting, Washington, D.C., Tues, Nov 28 – Fri, Dec 1, 2023.

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