SUO 2024: Home Instillation of UGN-102 for Primary Chemoablation of Recurrent Low-Grade Intermediate Risk NMIBC: A Single Arm, Open Label, Phase 3B Trial

(UroToday.com) The 2024 SUO annual meeting included a urothelial carcinoma session, featuring a presentation by Dr. Vincent Bivens discussing home instillation of UGN-102 for primary chemoablation of recurrent low-grade intermediate risk non muscle invasive bladder cancer (NMIBC). Bladder cancer is the 6th most common cancer in the US, with approximately 83,000 incident cases annually, and at diagnosis, 75% of patients present with NMIBC. Low grade, intermediate-risk NMIBC is a chronically relapsing disease, and the standard of care for its treatment is TURBT under general anesthesia. Recent experience suggests that many patients with low grade, intermediate-risk NMIBC can be successfully treated with UGN-102, a reverse thermal gel containing mitomycin administered via intravesical instillation in the outpatient setting, without the need for surgery [1-2]. At SUO 2024, Dr. Bivens and colleagues reported their experience of administering UGN-102 in the home, to examine the feasibility of treating selected individuals outside of the traditional venue for intravesical management of bladder cancer.

Key inclusion criteria were as follows:

  • Age >=18 years
  • Newly diagnosed or historical low grade, intermediate risk NMIBC (Ta) histologically confirmed by cold cup biopsy are screening or within 8 weeks before screening
  • Negative voiding cytology for high grade disease within 6 weeks before screening
  • Intermediate risk disease, defined as 1 or 2 of the following: multiple tumors, longest tumor diameter >3 cm, early or frequent recurrence (ie. >=1 episode within the previous year)

Enrolled patients received 6 weekly intravesical instillations of 75 mg UGN-102, a reverse thermal hydrogel containing mitomycin. The first treatment was administered at the investigative site, and the following 5 were administered at the patient’s home by a trained healthcare professional. Patients, healthcare professionals, and investigators completed questionnaires rating their experience after each home instillation and at the end of the study. The primary endpoint was feasibility, assessed as safety, discontinuation rate, and questionnaire feedback. The secondary endpoint was complete response (absence of bladder cancer) at the 3-month visit, determined by endoscopic evaluation, urine cytology, and for cause biopsy:

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Eight patients with low grade, intermediate-risk NMIBC meeting eligibility criteria were enrolled and treated with UGN-102. This included 6 patients (75.0%) that completed study-treatment (6 instillations), and 2 (25.0%) patients who discontinued treatment secondary to an adverse event. The median age was 75 years (range 55–84), most patients were male (62.5%), all were white, ad all had prior low grade NMIBC and had previously undergone TURBT. The median number of prior TURBTs was 4 (range 1–7), most patients had multiple tumors (62.5%), and 50.0% had a tumor burden >3 cm:

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Patients highly rated their home instillation experience for each domain of the patient questionnaire. Moreover, the median patient questionnaire scores remained the same throughout the treatment period, indicating that patients had no change in their home instillation experience over time:

  • Median comfort domain score: 12 (range: 10 – 12)
  • Median safety domain score: 4 (range: 3 – 4)
  • Median communication domain score: 8 (range: 6 – 8)
  • Median preference domain score: 4 (range: 2 – 4)
  • Median overall experience score: 4 (range: 3 – 4)
  • Median composite score: 32 (range: 26 – 32) 

Home instillation was reported as feasible by the visiting health care provider. At each instillation visit, the majority of available responses were in favor of home instillation, and most health care providers reported having no difficulty in performing it in the patient’s home:

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Most patients had mild-to-moderate adverse events that resolved or were resolving. Serious adverse events occurred in 3 patients, of which none were considered treatment-related:

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At the 3 month visit, 6 of the 8 participants achieved a complete response, with 2 patients who discontinued treatment counted as non-responders.

Dr. Bivens concluded his presentation by discussing home instillation of UGN-102 for primary chemoablation of recurrent low-grade intermediate risk NMIBC with the following take home messages:

  • Results from this small feasibility study demonstrate that home instillation of the chemoablation agent UGN-102 for the treatment of low grade, intermediate-risk NMIBC is feasible, convenient, and results in a clinically meaningful high complete response rate
  • The overall safety profile was consistent with that observed in the rest of the UGN-102 development program
  • Home instillation was rated highly by patients, healthcare professionals, and investigators
  • With trained home healthcare personnel, home instillation of UGN-102 may provide patients with a convenient alternative to in-clinic instillation, thus reducing the treatment burden

Presented by: Vincent Bivens, MD, Urology Centers of Alabama, Birmingham, AL

Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Associate Professor of Urology, Georgia Cancer Center, Wellstar MCG Health, @zklaassen_md on Twitter during the 2024 Society of Urologic Oncology (SUO) annual meeting held in Dallas, between the 3rd and 6th of December, 2024. 

References:

  1. Prasad SM, Huang WC, Shore ND, et al. Treatment of low-grade intermediate-risk nonmuscle-invasive bladder cancer with UGN-102 +/- transurethral resection of bladder tumor compared to transurethral resection of bladder tumor monotherapy: A randomized, controlled, phase 3 trial (ATLAS). J Urol. 2023 Oct;210(4):619-629.
  2. Prasad SM, Shishkov D, Mihaylov NV, et al. Primary chemoablation of recurrent low-grade intermediate-risk nonmuscle invasive bladder cancer with UGN-102: A single-arm, open-label, phase 3 trial (ENVISION). J Urol. 2024 Oct 24 [Epub ahead of print].