JU INSIGHT Efficacy of TAR-200 in Patients With Muscle-invasive Bladder Cancer

By: Mark D. Tyson, MD, MPH, Mayo Clinic Arizona, Phoenix; David Morris, MD, Urology Associates, Nashville, Tennessee; Juan Palou, MD, PhD, Fundacío Puigvert, Universitat Autònoma de Barcelona, Spain; Oscar Rodriguez, Fundacío Puigvert, Universitat Autònoma de Barcelona, Spain; Maria Carmen Mir, MD, PhD, Fundacío Puigvert, Universitat Fundacion Instituto Valenciano de Oncologia, Valencia, Spain; Rian J. Dickstein, MD, Chesapeake Urology, Baltimore, Maryland; Félix Guerrero-Ramos, MD, PhD, University Hospital 12 de Octubre, Madrid, Spain; Kristen R. Scarpato, MD, PhD, Vanderbilt University Medical Center, Nashville, Tennessee; Jason M. Hafron, MD, Michigan Institute of Urology, Troy; Edward M. Messing, MD, University of Rochester, New York; Christopher J. Cutie, MD, Janssen Research & Development, Lexington, Massachusetts; John C. Maffeo, MSHS, Janssen Research & Development, Lexington, Massachusetts; Bradley Raybold, MS, Janssen Research & Development, Springhouse, Pennsylvania; Albert Chau, Datacision Limited, London, United Kingdom; Katharine A. Stromberg, Janssen Research & Development, Raritan, New Jersey; Kirk A. Keegan, MD, MPH, Vanderbilt University Medical Center, Nashville, Tennessee, Janssen Research & Development, Lexington, Massachusetts | Posted on: 18 May 2023

Tyson MD, Morris D, Palou J, et al. Safety, tolerability, and preliminary efficacy of TAR-200 in patients with muscle-invasive bladder cancer who refused or were unfit for curative-intent therapy: a phase 1 study. J Urol. 2023;209(5):890-900.

Study Need and Importance

Standard-of-care treatment for muscle-invasive bladder cancer (MIBC) is platinum-based neoadjuvant chemotherapy followed by radical cystectomy or multimodal treatment combining maximal transurethral resection of bladder tumor with chemo/radiotherapy. However, half of patients with MIBC worldwide may not receive curative-intent therapy. Elderly or frail patients with MIBC are most affected by this unmet need.

TAR-200 is a novel intravesical drug delivery system that provides sustained, local release of gemcitabine into the bladder over a 21-day dosing cycle. This phase 1 study evaluated the safety, tolerability and preliminary efficacy of TAR-200 in patients with MIBC who either refused or were unfit for curative-intent therapy.

What We Found

Overall, 35 patients with MIBC who refused or were unfit for curative-intent therapy received at least 1 dose of TAR-200. Median age was 84 years and 46% had Eastern Cooperative Oncology Group performance status 3-4.

TAR-200 was generally safe and well tolerated. The most common TAR-200–related treatment-emergent adverse events (TEAEs) were dysuria and urinary frequency, generally observed at grades 1-2. Two patients experienced TEAEs leading to removal of TAR-200.

TAR-200 also showed preliminary signs of efficacy, with an overall response rate of 40.0% at 3 months, a median overall survival of 27.3 months, and a progression-free rate at 12 months of 70.5%.

Limitations

Our study is limited by its small sample size, single-arm design, and the absence of complete pathological assessment that would have been provided by radical cystectomy. Additionally, it is a challenge to distinguish whether TAR-200–related TEAEs were attributable to the drug, the delivery system, or the disease state, as this determination may be confounded.

Interpretation for Patient Care

The safety and preliminary efficacy data from this study support the continued development of TAR-200 across the bladder cancer spectrum. Multiple global, randomized, controlled phase 2/3 trials investigating TAR-200 are ongoing.