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

被引：115

作者：

Kleinmann, Nir ^{[1
]}

Matin, Surena F. ^{[2
]}

Pierorazio, Phillip M. ^{[3
]}

Gore, John L. ^{[4
]}

Shabsigh, Ahmad ^{[5
]}

Hu, Brian ^{[6
]}

Chamie, Karim ^{[7
]}

Godoy, Guilherme ^{[8
]}

Hubosky, Scott ^{[9
]}

Rivera, Marcelino ^{[10
]}

O'Donnell, Michael ^{[11
]}

Quek, Marcus ^{[12
]}

Raman, Jay D. ^{[13
]}

Knoedler, John J. ^{[13
]}

Scherr, Douglas ^{[14
]}

Stern, Joshua ^{[15
]}

Weight, Christopher ^{[16
]}

Weizer, Alon ^{[17
]}

Woods, Michael ^{[12
]}

Kaimakliotis, Hristos ^{[18
]}

Smith, Angela B. ^{[19
]}

Linehan, Jennifer ^{[20
]}

Coleman, Jonathan ^{[21
]}

Humphreys, Mitchell R. ^{[22
]}

Pak, Raymond ^{[23
]}

Lifshitz, David ^{[24
]}

Verni, Michael ^{[25
]}

Adibi, Mehrad ^{[2
]}

Amin, Mahul B. ^{[26
]}

Seltzer, Elyse ^{[27
]}

Klein, Ifat ^{[28
]}

Konorty, Marina ^{[28
]}

Strauss-Ayali, Dalit ^{[28
]}

Hakim, Gil ^{[28
]}

Schoenberg, Mark ^{[15
,27
]}

Lerner, Seth P. ^{[8
]}

机构：

[1] Sheba Med Ctr, Dept Urol, Ramat Gan, Israel

[2] Univ Texas MD Anderson Canc Ctr, Dept Urol, Houston, TX 77030 USA

[3] Johns Hopkins Univ, Brady Urol Inst, Baltimore, MD USA

[4] Univ Washington, Dept Urol, Med Ctr, Seattle, WA 98195 USA

[5] Ohio State Univ, Ctr Comprehens Canc, Dept Urol, Columbus, OH 43210 USA

[6] Loma Linda Univ, Dept Urol, Loma Linda, CA 92350 USA

[7] Univ Calif Los Angeles, Dept Urol, Los Angeles, CA USA

[8] Baylor Coll Med, Dept Urol, Houston, TX 77030 USA

[9] Thomas Jefferson Univ Hosp, Sidney Kimmel Med Coll, Dept Urol, Philadelphia, PA 19107 USA

[10] Mayo Clin Hlth Syst, Dept Urol, Rochester, MN USA

[11] Univ Iowa, Dept Urol, Iowa City, IA 52242 USA

[12] Loyola Univ Med Ctr, Dept Urol, Maywood, IL 60153 USA

[13] Penn State Hlth Milton S Hershey Med Ctr, Div Urol, Hershey, PA USA

[14] Cornell Univ, Dept Urol, Weill Med Coll, New York, NY 10021 USA

[15] Albert Einstein Coll Med, Dept Urol, Bronx, NY 10467 USA

[16] Univ Minnesota Hlth, Dept Urol, Minneapolis, MN USA

[17] Univ Michigan, Dept Urol, Ann Arbor, MI 48109 USA

[18] Indiana Univ Sch Med, Dept Urol, Indianapolis, IN 46202 USA

[19] Univ N Carolina, Sch Med, Dept Urol, Chapel Hill, NC 27515 USA

[20] John Wayne Canc Inst, Dept Urol, Santa Monica, CA USA

[21] Mem Sloan Kettering Canc Ctr, Dept Urol, 1275 York Ave, New York, NY 10021 USA

[22] Mayo Clin Phoenix, Dept Urol, Scottsdale, AZ USA

[23] Mayo Clin Jacksonville, Dept Urol, 4500 San Pablo Rd, Jacksonville, FL 32224 USA

[24] Rabin Med Ctr, Dept Urol, Tel Aviv, Israel

[25] Urol Ctr Las Vegas, Las Vegas, NV USA

[26] Univ Tennessee, Ctr Hlth Sci, Dept Pathol, Memphis, TN 38163 USA

[27] UroGen Pharma, New York, NY USA

[28] UroGen Pharma, Raanana, Israel

来源：

LANCET ONCOLOGY | 2020年 / 21卷 / 06期

关键词：

UPPER URINARY-TRACT; RADICAL NEPHROURETERECTOMY; CELL-CARCINOMA; DRUG-DELIVERY; TRENDS; AGE;

D O I：

10.1016/S1470-2045(20)30147-9

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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<0.0001) patients had a complete response at the primary disease evaluation visit. The median follow-up for patients with a complete response was 11.0 months (IQR 5 .1-12. 4). The most frequently reported all-cause adverse events were ureteric stenosis in 31 (44%) of 71 patients, urinary tract infection in 23 (32%), haematuria in 22 (31%), flank pain in 21 (30%), and nausea in 17 (24%). 19 (27%) of 71 patients had study drug-related or procedure-related serious adverse events. No deaths were regarded as related to treatment. 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. Copyright (C) 2020 Elsevier Ltd. All rights reserved.

引用

页码：776 / 785

页数：10

共 32 条

[1] An Analysis of Staging and Treatment Trends for Upper Tract Urothelial Carcinoma in the National Cancer Database [J].