Primary chemoablation of low-grade upper tract urothelial carcinoma using UGN-101, a mitomycin-containing reverse thermal gel (OLYMPUS): an open-label, single-arm, phase 3 trial.
The lancet oncology
Adult; Aged; Aged, 80 and over; Antibiotics, Antineoplastic; Carcinoma; Drug Carriers; Drug Compounding; Female; Humans; Hydrogels; Israel; Kidney Neoplasms; Male; Middle Aged; Mitomycin; Neoplasm Grading; Time Factors; Treatment Outcome; United States; Urothelium
BACKGROUND: Most patients with low-grade upper tract urothelial cancer are treated by radical nephroureterectomy. We aimed to assess the safety and activity of a non-surgical treatment using instillation of UGN-101, a mitomycin-containing reverse thermal gel.
METHODS: In this open-label, single-arm, phase 3 trial, participants were recruited from 24 academic sites in the USA and Israel. Patients (aged ≥18 years) with primary or recurrent biopsy-proven, low-grade upper tract urothelial cancer (measuring 5-15 mm in maximum diameter) and an Eastern Cooperative Oncology Group performance status score of less than 3 (Karnofsky Performance Status score >40) were registered to receive six instillations of once-weekly UGN-101 (mitomycin 4 mg per mL; dosed according to volume of patient's renal pelvis and calyces, maximum 60 mg per instillation) via retrograde catheter to the renal pelvis and calyces. All patients had a planned primary disease evaluation 4-6 weeks after the completion of initial therapy, in which the primary outcome of complete response was assessed, defined as negative 3-month ureteroscopic evaluation, negative cytology, and negative for-cause biopsy. Activity (complete response, expected to occur in >15% of patients) and safety were assessed by the investigator in all patients who received at least one dose of UGN-101. Data presented are from the data cutoff on May 22, 2019. This study is registered with ClinicalTrials.gov, NCT02793128.
FINDINGS: Between April 6, 2017, and Nov 26, 2018, 71 (96%) of 74 enrolled patients received at least one dose of UGN-101. 42 (59%, 95% CI 47-71; p
INTERPRETATION: Primary chemoablation of low-grade upper tract urothelial cancer with intracavitary UGN-101 results in clinically significant disease eradication and might offer a kidney-sparing treatment alternative for these patients.
FUNDING: UroGen Pharma.
Kleinmann, Nir; Matin, Surena F; Pierorazio, Phillip M; Gore, John L; Shabsigh, Ahmad; Hu, Brian; Chamie, Karim; Godoy, Guilherme; Hubosky, Scott; Rivera, Marcelino; O'Donnell, Michael; Quek, Marcus; Raman, Jay D; Knoedler, John J; Scherr, Douglas; Stern, Joshua; Weight, Christopher; Weizer, Alon; Woods, Michael; Kaimakliotis, Hristos; Smith, Angela B; Linehan, Jennifer M; Coleman, Jonathan; Humphreys, Mitchell R; Pak, Raymond; Lifshitz, David; Verni, Michael; Adibi, Mehrad; Amin, Mahul B; Seltzer, Elyse; Klein, Ifat; Konorty, Marina; Strauss-Ayali, Dalit; Hakim, Gil; Schoenberg, Mark; and Lerner, Seth P, "Primary chemoablation of low-grade upper tract urothelial carcinoma using UGN-101, a mitomycin-containing reverse thermal gel (OLYMPUS): an open-label, single-arm, phase 3 trial." (2020). Articles, Abstracts, and Reports. 3406.