This article is more than 5 years old. Information may no longer be current.
UGN-101 active in unresectable upper tract urothelial cancer
Click Here to Manage Email Alerts
UGN-101 gel induced complete response in a majority of patients with endoscopically unresectable low-grade upper tract urothelial cancer, according to results of the phase 3 OLYMPUS trial presented at American Urological Association Annual Meeting.
The responses with UGN-101 (UroGen Pharma) — an investigational formulation of mitomycin delivered via standard intravesical catheters — also appeared durable.
“I continue to be very encouraged, though not surprised, by these findings,” Karim Chamie, MD, MSHS, associate professor-in-residence of urology at UCLA Health, told HemOnc Today. “Based on the entirety of data observed from the OLYMPUS trial to date, I’m optimistic that UGN-101 has the potential to change the treatment paradigm for patients with low-grade upper tract urothelial cancer.”
Low-grade upper tract urothelial cancer is a rare malignant tumor of the cells that line the urinary tract. It is most common among elderly individuals who have comorbid conditions, such as diabetes, obesity, hypertension and metabolic syndrome.
Standard treatment typically consists of complete removal of the kidney and/or partial removal of the ureter. Repetitive endoscopic tumor resection is used when feasible for patients with limited tumor burden.
These surgical interventions carry risks for infection and bleeding, as well as injury to adjacent organs and potential long-term morbidity associated with removal of the kidney.
UGN-101 — a sustained release, hydrogel-based formulation that has received breakthrough, fast track and orphan drug designations from FDA — is intended to allow for longer exposure of mitomycin to the urinary tract tissue, enabling treatment of tumors by means other than surgery.
The open-label, single-arm OLYMPUS trial evaluated the safety, tolerability and tumor-ablative effect of UGN-101 for patients with low-grade upper tract urothelial cancer. Researchers enrolled patients at sites across the United States and Israel.
Study participants received six weekly instillations of UGN-101.
Primary disease evaluation performed 4 to 6 weeks after the final instillation measured response, the study’s primary endpoint. This evaluation included ureteroscopy and wash cytology.
Patients who achieved complete response by the time of primary disease evaluation remained in follow-up for 1 year to assess durability of disease control.
The intention-to-treat analysis included 71 patients who underwent primary disease evaluation; 42 (59%) of these patients achieved complete response and 41 entered follow-up.
Twenty-seven patients who achieved complete response had undergone 6-month evaluation at the time of data cutoff. Twenty-four (89%) of them remained disease free at 6 months, which Chamie described as “a significant finding.”
Among the 34 patients initially characterized by the treating physician as having endoscopically unresectable tumor at baseline, 20 (59%) achieved complete response at primary disease evaluation and 17 (85%) remained disease free at 6 months.
Only five of the 41 patients who achieved complete response relapsed during the study period.
“Given the anatomical complexity of the kidney and the physical limits of endoscopic instrumentation, treatment of low-grade upper tract urothelial cancer remains a technical challenge for many urologists,” Chamie told HemOnc Today. They “continue to struggle with treating patients with ... the less-than-desirable standard of care, which requires surgical intervention, putting these patients at risk for complications associated with repetitive endoscopic surgical procedures, recurrences within the kidney and ureter, and — ultimately — kidney removal.
“In fact, nearly 80 percent of patients with low-grade upper tract urothelial cancer will undergo kidney removal at some point during their treatment,” Chamie added. “The availability of an alternative, minimally-invasive treatment could be game-changing for physicians.”
The most common adverse events reported in the study included urinary tract infection, ureteral narrowing and stricture formation.
“These side effects are also seen when patients undergo endoscopic tumor ablation,” Chamie said. “UGN-101 appeared to be well-tolerated, with most treatment-related adverse events characterized as mild or moderate and transient in nature.”
A 5-day course of steroids significantly helps with transient ureteral narrowing, and no patients required surgical intervention for this condition, Chamie said.
He described the progress seen with UGN-101 as “an important and exciting step” in urologic oncology, noting there are no FDA-approved drugs for treatment of low-grade upper tract urothelial cancer.
“These patients, who are generally elderly, bear a great burden with kidney removal surgery,” Chamie told HemOnc Today. “They are subject to a multitude of short-term risks, such as bleeding, infection and injury to adjacent organs, all against the backdrop of common comorbidities such as hypertension, diabetes, cardiac disease and obesity.
“Renal preservation in this population would address a significant unmet medical need,” Chamie added. “ If UGN-101 is approved, it will bring kidney preservation to the frontline management of care for patients who typically have no viable options but kidney removal.” – by Mark Leiser
Reference: Kleinmann N, et al. Abstract 19-9773. Presented at: American Urological Association Annual Meeting; May 3-6, 2019; Chicago.
Disclosure: Chamie reports a consultant role with UroGen Pharma. Please see the abstract for all other authors’ relevant financial disclosures.