乌鸦传媒

WASHINGTON -- An investigational non-surgical treatment led to a "robust" complete response rate in patients with recurrent, low-grade non-muscle-invasive bladder cancer, the phase III ENVISION study showed.

Patients treated with the UGN-102 (mitomycin) intravesical solution achieved a complete response rate of 79.2% (95% CI 73.5-84.1) at 3 months without having to undergo transurethral resection of bladder tumors (TURBT), reported Sandip Prasad, MD, MPhil, of the Morristown Medical Center/Atlantic Health System in New Jersey.

"If approved, UGN-102 would become the first non-surgical option for patients with low-grade, intermediate-risk non-muscle-invasive bladder cancer," Prasad said during a late-breaking abstract session at the Society of Urologic Oncology annual meeting, "and I would argue it would potentially be a paradigm shift in the way we treat and evaluate these patients going forward."

The ENVISION study population "is really a cumbersome one for urologists," he explained. "It's this group of patients who have low-grade disease, but with intermediate risk." This study focused on highly recurrent patients, he added, meaning they have more than one recurrence of tumor within 12 months.

"These patients have common recurrences and undergo TURBT frequently," he said. "Unfortunately for these patients that often requires discontinuation of systemic anticoagulation, and general anesthesia. And these repetitive TURBTs can lead to both short-term and long-term morbidity, as well as increased mortality, which has been demonstrated in numerous studies."

While there are currently available options to attempt to minimize recurrences -- the most common of which is adjuvant chemotherapy following TURBT -- Prasad observed that overall adoption and compliance with this strategy is low.

"So we are left with what people have described as an 'orphan space,'" he added. "We have no approved primary non-surgical options for these highly recurrent, low-grade patients."

UGN-102 is an investigational drug formulation of mitomycin. With the use of RTGel technology -- a sustained-release, hydrogel-based formulation -- UGN-102 is designed to enable longer exposure of bladder tissue to mitomycin.

In explaining its mechanism of action, Prasad said the formulation coats the entirety of the urothelial surface.

"Fundamentally, it's using mitomycin -- chemotherapy -- but impregnated with a reverse thermal gel that allows for installation into the bladder and maintenance of continuity of mitomycin for longer periods of time," he explained. Specifically, he pointed out that the RTGel inherently allows for adherence of the mitomycin to the urothelium on its own and isn't excreted with voiding.

"In fact, patients can void several times and have continued adherence, allowing the drug to maintain contact with the surface, typically for about 6 hours," he said.

is a single-arm, multinational, multicenter study that includes 240 patients who received weekly installation of the study drug for 6 weeks through a traditional urethral catheter. Patients were then evaluated at 3 months with cystoscopy.

Median patient age was 70 years, and the majority were men and white. Nearly all (95%) of the patients received all six installations of the study drug.

Prasad noted that UGN-102 non-responders underwent TURBT, and of those patients, just 2.5% progressed to high-grade disease. "So, in general, even for the one-fifth of patients who were not complete responders, there was no significant clinical compromise to being a non-responder for this treatment," he said.

Regarding safety, the most common adverse event was dysuria, with most cases being mild to moderate, and which Prasad said is to be expected with patients who have undergone cystoscopy and six intravesical catheter installations.

One patient developed a urethral stricture during treatment, and one developed urinary retention. There were no serious treatment-related adverse events or deaths.

The secondary endpoint of duration of response continues to be studied, Prasad said.

Comment