EAU 2022: State-of-the-art Lecture Landscape of Current Trials with Intravesical Treatment in High Risk BCG naïve NMIBC

(UroToday.com) The 37th Annual European Association of Urology Congress held in Amsterdam, Netherlands between July 1st,and 4th 2022 was host to a plenary session on perioperative treatment of urothelial cancers in 2022. Dr. Ashish Kamat expertly discussed the landscape of current trials with intravesical treatment in high-risk BCG naïve non-muscle invasive bladder cancer (NMIBC).


Dr. Kamat began his presentation by discussing the recent changes in the EAU NMIBC risk stratification from 2020 to 2021. He highlighted that any patient with HG disease, even Ta, is now considered a “high risk” NMIBC. While this may not necessarily have significant clinical implications at the current time, particularly when counseling our patients regarding treatment options, this is of utmost significance when designing clinical trials in the BCG-naïve space.

He next went on to discuss the current EAU model for predicting therapeutic response to BCG. The currently available EAU NMIBC risk calculator significantly overpredicts the risk of disease progression by risk group for BCG-treated patients. In fact, Dr. Kamat’s group recently published on this subject matter in European Urology Oncology. Patients in the very-high-risk group receiving adequate BCG had a one-year progression rate of 4.0% versus the EAU predicted rate of 16.0%. The five-year progression rate for patients in the high-risk group was 5.3% versus 9.6% for EAU predicted rates.1

He next went on to emphasize again the importance of classifying all HGTa diseases as high risk NMIBC. A recent report by his group demonstrated that HGTa patients regardless of whether “intermediate-risk” HG Ta or “high-risk” HG Ta had similar rates of disease progression ≥T2: 5.9% and 6.5%; T1: 13% and 13%, respectively.2


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Current/emerging pharmaceutically available intravesical treatment options include:

  • RTGel formulation of mitomycin by UroGen® (UGN-102)
  • TARIS® GemRIS: An implantable drug delivery system that delivers continuous intravesical gemcitabine
  • Hyperthermic intravesical chemotherapeutic option by COMBAT BRS Medical® and SYNERGO®

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Intravesical treatment with gemcitabine and docetaxel holds great promise in the NMIBC space. A multi-institutional retrospective analysis of 276 patients with NMIBC and previous BCG treatment demonstrated that intravesical gemcitabine/docetaxel had promising one and two-year recurrence-free survival rates of 60% and 46%, and high-grade recurrence-free survival rates of 65% and 52%, respectively.3

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Conversely in the BCG naïve, high-risk NMIBC space, McElree et al. recently reported results of gemcitabine/docextaxel for BCG naïve, high-risk NMIBC with promising two-year high-grade RFS rates of 84% after a median follow-up of 15 months.


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While the FDA approved single arm trials in the BCG-resistant NMIBC space due to the lack of an acceptable gold standard treatment option, the same does not hold true for the BCG-naïve space. Any trial in this disease space needs to be compared to the current gold standard of BCG. As such, we await the results of the non-inferiority BRIDGE trial which stratifies BCG-naïve NMIBC patients to gemcitabine/docetaxel versus BCG, with a primary endpoint of event free survival.

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Prospective, single arm, observational data from Spain has demonstrated the utility of hyperthermic intravesical chemotherapy (HIVEC) with mitomycin and a COMBAT® bladder recirculation system in NMIBC patients:


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The SUNRISE-3 is a phase 3 trial of TAR-200 (intravesical drug-delivery system designed for local continuous release of gemcitabine intravesically) + Cetrelimab (PD-1 inhibitor) versus intravesical BCG in BCG naïve (or previously treated greater than 3 years ago) with primary endpoints of event-free survival and, for CIS patients, complete response.

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Dr. Kamat noted that we continue to await the results of the POTOMAC trial, a phase 3 trial in BCG-naïve, high-risk NMIBC patients who are randomized to (i) BCG induction + 24 month maintenance versus (ii) BCG induction + 24 month maintenance + Durvalumab versus (iii) BCG induction alone + Durvalumab, with a primary endpoint of DFS

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A phase 1 trial of intravesical pembrolizumab + BCG in patients with BCG-unresponsive NMIBC recruited 9 patients (closed early due to COVID) with RFS of 66% at 6 months and 22% at one year.


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Results from the Phase 1/2 LEGEND trial has shown promising results for EG-70, a dual RIG-I agonist/IL-12 local gene therapy in BCG-unresponsive NMIBC.

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N-803 (Anktiva), a novel IL-15 superagonist fusion protein that upregulates NK and T Cells, has shown very promising results in combination with BCG in the QUILT 3032 phase 2/3 study, presented at ASCO 2022, in previously BCG-unresponsive bladder cancer with complete response rates of 71% and median duration of response of 26.6 months.


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Verity VPM1002, a genetically modified BCG variant, is also an emerging treatment option in this disease space.

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Dr. Kamat concluded his presentation by again emphasizing the importance of classifying all HG Ta tumors as high risk NMIBC for the purpose of clinical trials design and that any trial in the BCG naïve space must have a control arm. BCG remains an excellent treatment option in this disease space and remains the “one to beat” in 2022.


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Presented by: Dr. Ashish M. Kamat, MD, MBBS, Endowed Professor of Urologic Oncology (Surgery) and Cancer Research, Department of Urology, University of Texas MD Anderson Cancer Center, Houston, TX

Written by: Rashid Sayyid, MD, MSc – Society of Urologic Oncology (SUO) Clinical Fellow at The University of Toronto, @rksayyid on Twitter during the 2022 European Association of Urology (EAU) Annual Hybrid Meeting, Amsterdam, NL, Fri, July 1 – Mon, July 4, 2022.

  1. Lobo N, et al. Updated European Association of Urology (EAU) Prognostic Factor Risk Groups Overestimate the Risk of Progression in Patients with Non-muscle-invasive Bladder Cancer Treated with Bacillus Calmette-Guérin. Eur Urol Oncol. 2022;5(1):84-91.
  2. Bree KK, et al. All High-Grade Ta Tumors Should Be Classified as High Risk: Bacillus Calmette-Guérin Response in High-Grade Ta Tumors. J Urol. 2022.
  3. Steinberg RL, et al. Multi-Institution Evaluation of Sequential Gemcitabine and Docetaxel as Rescue Therapy for Nonmuscle Invasive Bladder Cancer. J Urol. 2020;203(5):902-909.



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