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PEER-TO-PEER CLINICAL CONVERSATIONS |
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BCG Unresponsive Bladder Cancer in 2024
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Ashish Kamat, MD, MBBS
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| Zachary Klaassen and Ashish Kamat explore the evolving landscape of BCG-unresponsive bladder cancer treatment. Dr. Kamat traces the development of treatment options from the establishment of BCG-unresponsive disease criteria to the current array of approved and emerging therapies, including pembrolizumab, nadofaragene, and newer agents like TAR-200 and cretostimogene.
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| PIVOT-006: Phase III Trial of Creto vs Surveillance in Intermediate-Risk Bladder Cancer |
| Mark Tyson II, MD, MPH |
| A discussion between Zachary Klaassen and Mark Tyson explores the PIVOT-006 trial examining cretostimogene versus surveillance for intermediate-risk non-muscle invasive bladder cancer. The study evaluates this oncolytic immunotherapy in a new patient population, focusing on both low-grade and high-grade disease that meets specific AUA criteria for intermediate risk. |
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| Current Options for BCG Unresponsive NMIBC |
| Eugene Pietzak, MD |
| Sam Chang hosts Eugene Pietzak to discuss treatment options for BCG-unresponsive bladder cancer and the challenges of evaluating their comparative effectiveness. Dr. Pietzak emphasizes that while multiple FDA-approved treatments are now available, including pembrolizumab, nadofaragene, and BCG with IL-15 superagonist, comparing their efficacy is complicated by variations in trial designs, surgeon techniques, pathology interpretations, and patient populations. |
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HIGHLIGHTS FROM THE 2024 SOCIETY OF UROLOGIC ONCOLOGY ANNUAL MEETING |
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| Topline Results from BOND-003: A Phase-3 Study of Intravesical Cretostimogene Grenadenorepvec for the Treatment of High-Risk BCG-Unresponsive NMIBC with CIS
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| Mark Tyson II, MD, MPH |
| Mark Tyson presented results from BOND-003, a phase III trial evaluating cretostimogene grenadenorepvec for the treatment of high-risk, BCG-unresponsive non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS). This oncolytic immunotherapy showed a promising complete response rate of 74.5% at any time. At 12 months, the response rate was 46-50%, with 97.3% of patients remaining free from progression to muscle-invasive disease. Notably, the therapy was well tolerated with no grade ≥3 treatment-related adverse events. |
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| The Impact of BCG Shortage on Disease Recurrence for Patients with Non-Muscle Invasive Bladder Cancer: A SEER Patterns of Care Analysis
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| Madison M. Wahlen
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| A SEER-based analysis presented at SUO 2024 evaluated the impact of BCG shortages on recurrence-free survival in NMIBC patients, finding no increased hazard of recurrence due to the shortages. Patients who received BCG had a significantly reduced recurrence risk (HR 0.46), underscoring its effectiveness. Alternative strategies like BCG dose reduction may mitigate shortages without compromising outcomes, supporting continued risk-adapted utilization.
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| Mechanism of Action and Translation to the Clinic of Detalimogene Voraplasmid (EG-70) – A Novel, Investigational Non-Viral Immunotherapy for NMIBC |
| Anthony Cheung |
| At SUO 2024, Dr. Anthony Cheung presented findings on detalimogene voraplasmid (EG-70), a novel intravesical non-viral immunotherapy designed for BCG-unresponsive NMIBC. Preclinical data demonstrated its ability to remodel the tumor microenvironment from immunosuppressive to pro-inflammatory, driving tumor clearance and long-lasting immune memory. In the LEGEND phase 1 study, a 73% complete response rate was observed with a favorable safety profile, suggesting robust efficacy and tolerability. Phase 2 trials are underway to further explore its clinical utility. |
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| ADVANCED-2: Phase 2 Open-Label Study to Evaluate Safety and Anti-Tumor Activity of Intravesical Instillation of TARA-002 in Adults with High-Grade Non-Muscle Invasive Bladder Cancer |
| Brian Mazzarella, MD, FACS |
| Brian Mazzarella presented results from ADVANCED-2, a Phase 2 study evaluating the safety and efficacy of TARA-002, an investigational intravesical immunotherapy for high-grade NMIBC. TARA-002 leverages broad-spectrum immune potentiation via a TH1 pro-inflammatory cytokine response and is being studied in both BCG-naïve and BCG-unresponsive populations. |
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| Utility of Rescue Bacillus Calmette-Guerin Therapy in Treatment of BCG-Unresponsive Non-Muscle Invasive Bladder Cancer
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| Ketty Bai, BS
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| Ketty Bai presented a retrospective analysis on the utility of rescue Bacillus Calmette-Guérin (BCG) therapy in BCG-unresponsive NMIBC. The study found no significant differences in progression-free survival, high-grade recurrence-free survival, or overall survival between patients treated with rescue BCG and those who received alternative therapies such as intravesical chemotherapy or surgery. However, rescue BCG was associated with a decreased risk of progression after adjusting for confounders, highlighting its potential as a cost-effective alternative in select high-risk patients.
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| Primary Chemoablation of Recurrent Low-Grade Intermediate-Risk NMIBC with UGN-102: A Single Arm, Open Label, Phase 3 Trial (ENVISION)
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| Sandip M. Prasad, MD
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| Sandip Prasad presented findings from the Phase 3 ENVISION trial, which evaluated UGN-102, a chemoablative reverse thermal gel containing mitomycin, for treating recurrent low-grade intermediate-risk NMIBC. The trial demonstrated a 79.6% complete response rate at three months, with a durable response observed in 82.3% of responders remaining event-free at 12 months. Adverse events were generally mild to moderate, with serious events reported in 12% of patients.
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| Home Instillation of UGN-102 for Primary Chemoablation of Recurrent Low-Grade Intermediate-Risk NMIBC: A Single Arm, Open Label, Phase 3B Trial
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| Vincent Bivens, MD
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| Vincent Bivens presented a Phase 3B trial evaluating home administration of UGN-102, a reverse thermal gel containing mitomycin, for treating recurrent low-grade intermediate-risk NMIBC. In this small feasibility study, 75% of patients completed all six weekly home instillations, demonstrating a high 75% complete response rate at three months. Patients, healthcare professionals, and investigators rated the home administration process highly for comfort and convenience, with most adverse events being mild to moderate.
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| BOND-003 Cohort P: A Multi-national, Single-arm Study of Intravesical Cretostimogene Grenadenorepvec for the Treatment of High-Risk, Papillary Only, BCG-Unresponsive Non-Muscle Invasive Bladder Cancer |
| Mark Tyson II, MD, MPH |
| Mark Tyson presented the BOND-003 Cohort P study, which evaluates the use of intravesical cretostimogene grenadenorepvec in treating BCG-unresponsive high-risk NMIBC patients with Ta/T1 tumors without carcinoma in situ (CIS). This multi-national, single-arm trial aims to assess the efficacy and safety of cretostimogene, an oncolytic immunotherapy, in a population that traditionally faces limited bladder-sparing treatment options. Preliminary results from the study are anticipated to address the significant unmet need for well-tolerated therapies in this patient group. |
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| PIVOT-006: A Phase 3, Randomized Study of Adjuvant Intravesical Cretostimogene Grenadenorepvec versus Surveillance for the Treatment of Intermediate-Risk Non-Muscle Invasive Bladder Cancer |
| Robert Svatek, MD, MSCI |
| Robert Svatek presented findings from the PIVOT-006 trial, a randomized, phase 3 study evaluating adjuvant intravesical cretostimogene grenadenorepvec against standard surveillance for patients with intermediate-risk non-muscle invasive bladder cancer (NMIBC). The study addresses an unmet need for improved adjuvant therapies in this patient population, which faces recurrence rates of 30–60% under current management approaches. |
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| Low-Grade and High-Grade Intermediate-risk Non-Muscle Invasive Bladder Cancers Respond Differently to Bacillus Calmette-Guerin and Gemcitabine-Docetaxal
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| Ahmed Eraky, MBBCh, FEBU
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| Ahmed Eraky presented a retrospective analysis comparing the efficacy of intravesical Bacillus Calmette-Guérin (BCG) versus gemcitabine + docetaxel in treating low- and high-grade intermediate-risk non-muscle invasive bladder cancer (NMIBC). This study addressed the need for alternative treatments due to the global BCG shortage.
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| Moonrise-1: Phase 3 Study of TAR-210, an Erdafitinib Intravesical Targeted Releasing System, Versus Intravesical Chemotherapy in Patients with FGFR-Altered Intermediate Risk Non-Muscle Invasive Bladder Cancer
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| Roger Li, MD
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| The Moonrise-1 phase 3 study presented at SUO 2024 evaluates the efficacy of TAR-210, an intravesical targeted releasing system delivering erdafitinib, against standard intravesical chemotherapy (mitomycin C or gemcitabine) in patients with FGFR-altered intermediate-risk NMIBC. This randomized trial, involving around 540 patients, aims to assess disease-free survival as the primary endpoint, with secondary outcomes including progression-free survival and high-grade recurrence-free survival. Preliminary data suggest TAR-210 offers promising clinical activity with minimal systemic toxicity.
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| Incidence and Pathologic Outcomes of Cystectomy in Patients with BCG-Unresponsive NMIBC with CIS Following Treatment with Nadofaragene Firadenovec |
| Vikram M. Narayan, MD |
| Vikram Narayan presented findings from the CS-003 phase 3 study, evaluating nadofaragene firadenovec for BCG-unresponsive NMIBC with CIS ± Ta/T1. Results showed that 42.7% of participants underwent cystectomy, with 6 cases of muscle invasive bladder cancer and a median cystectomy-free survival of 47.9 months for all participants. Those who achieved a complete response at 3 months had a significantly longer cystectomy-free survival compared to non-responders, suggesting that nadofaragene firadenovec can effectively delay cystectomy without compromising cure potential. |
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