Twenty percent of patients (n = 3) did not have a lasting response due to disease recurrence (13%; n = 2). One patient had to undergo radical nephro-ureterectomy (7%); however, in particular, this was achieved due to a narrowing of the ureter rather than a recurrence of the disease.
Patients who had a recurrence underwent endoscopic ablation. None of the patients with disease recurrence progressed to high-grade disease. At the last follow-up, the disease-specific survival rate was 100%.
“UGN-101 demonstrates long-term durability that exceeds that obtained with renal sparing options like laser ablation,” said lead author of the trial Karim Chamie, MD, MSHS, associate professor of urology at the University of California, Los Angeles, in a data presentation. “With laser ablation therapies, we have seen [from] pooled analyzes of previous publications recidivism rates [were] more than 65% with a median follow-up of 43 months.
LG-UTUC is a rare disease for which treatment options are limited. Despite the significant advances made with endoscopic therapies, most patients still have to undergo radical nephro-ureterectomy, according to Chamie, who added that data from population-level analyzes indicate that up to 70% of patients with d ‘low-grade non-invasive disease undergo even more extirpative surgery. .
Advances in the field of endoscopic surgeries have made it possible to save several kidneys. However, the results of a pooled analysis of 597 patients, 78% of whom had low or intermediate grade disease, demonstrated that 65% of the population had disease recurrence after ureteroscopic treatment at a median follow-up of 43 months (range: 24 -58) .2 “That’s pretty important,” noted Chamie.
Thus, the investigators initiated the phase 3 OLYMPUS trial to evaluate UGN-101. Previous study results culminated in the April 2020 publication FDA Approval of Mitomycin Gel for the Treatment of Patients with LG-UTUC.3 Previous reports have estimated the durability of the response rate of 84% at 12 months in those who achieved a complete response (CR) after UGN-101 induction therapy.
The open-label, single-arm phase 3 trial included a total of 71 patients with LG-UTUC who had never received treatment or had low-grade, non-invasive recurrent disease with at least 1 measurable papillary tumor.
Study participants received UGN-101 once a week for 6 weeks, followed by a grace period of 4 to 6 weeks, according to Chamie. During this period, patients were assessed for the primary efficacy endpoint of CR rate at their primary disease assessment (PDE) visit. If patients had CR on treatment, they received the gel every month for up to an additional 11 months.
“Patients were determined to have CR if the ureteroscopy and cytology were completely normal,” Chamie explained. “If there were any abnormalities, the patients underwent a biopsy which was determined to be a recurrence or CR.”
A key secondary endpoint of the trial was the durable response at the 12-month follow-up visit, and other endpoints included the durability of the response with UGN-101 at 3, 6 and 9 months after the EDP visit. As part of long-term follow-up, investigators looked at duration of response, disease recurrence, disease progression, and death.
The primary analysis of the trial was performed on the intention-to-treat (ITT) population, which included patients who received one or more instillations of the gel. Secondary analyzes were performed in patients who achieved CR at the time of their PDE visit, and long-term follow-up analyzes focused on those who had CR 12 months after their PDE visit.
Of the 71 patients included in the study (ITT population), 10 discontinued UGN-101 (9 due to adverse effects [AEs] and 1 due to withdrawal of consent), and 19 did not obtain a CR during their PDE visit. A total of 42 patients in the ITT population experienced treatment CR at the time of their PDE visit, resulting in a CR rate of 59.2% (95% CI, 46.8% -70 , 7%). Of these patients, 1 withdrew consent, 10 discontinued treatment, and 8 experienced disease recurrence.
Twenty-three patients maintained their CR at 12 months, resulting in a CR rate of 56.1% (95% CI, 39.7% to 71.5%). Five of these patients were in sites where the follow-up protocol had not yet been initiated, 2 had no data available and 1 was lost to follow-up. At the AAU 2021 annual meeting, Chamie shared data on the remaining 15 evaluable patients.
Limitations of the study included a small sample size and missing data for 8 of 23 patients who had lasting responses 12 months after their EDP visit, Chamie concluded.