JU INSIGHT A Phase 2 Trial of Intravesical Gemcitabine and Docetaxel for BCG-Naïve Nonmuscle-Invasive Bladder Cancer

By: Sunil H. Patel, MD, James Buchanan Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland; Andrew T. Gabrielson, MD, James Buchanan Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland; Sin Chan, BS, James Buchanan Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland; Deborah Schwartz, RN, BSN, James Buchanan Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland; Connie Collins, RN, James Buchanan Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland; Nirmish Singla, MD, MSc, James Buchanan Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland; Bruce Trock, PhD, James Buchanan Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland; Trinity J. Bivalacqua, MD, PhD, Hospital of the University of Pennsylvania, Philadelphia; Noah Hahn, MD, James Buchanan Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland Greenberg Bladder Cancer Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland; Max R. Kates, MD, James Buchanan Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland | Posted on: 17 Jul 2024

Patel SH, Gabrielson AT, Chan S, et al. A phase 2 trial of intravesical gemcitabine and docetaxel in the treatment of bacillus Calmette-Guérin–naïve nonmuscle-invasive urothelial carcinoma of the bladder. J Urol. 2024;212(1):95-103. doi:10.1097/ JU. 0000000000003977

Study Need and Importance

For decades, the mainstay treatment for patients with high-risk nonmuscle-invasive bladder cancer (NMIBC) has been intravesical treatment with bacillus Calmette-Guérin (BCG). However, amidst widespread BCG shortages researchers have sought alternative treatment options that can be utilized in the BCG-naïve setting. Combination intravesical gemcitabine and docetaxel (GemDoce) has demonstrated efficacy as a second-line therapy for patients with BCG-unresponsive NMIBC. In this context, we performed a prospective single-arm open-label phase 2 trial for patients with BCG-naïve high-risk NMIBC. Intravesical GemDoce was administered weekly for 6 weeks as induction followed by monthly maintenance therapy for 2 years among responders. The primary end point was 3-month complete response rate, and secondary end points included adverse events (AEs) and 12-month complete response rate.

What We Found

Between August 2020 and August 2022 we enrolled 25 patients with median follow-up of 19.6 months. The pretreatment pathologic stages were high-grade (HG) T1 with carcinoma in situ (CIS; n=7), HGT1 without CIS (n=6), HGTa (n=9), and CIS alone (n=3). The 3-month and 12-month CR rates were 100% and 92%, respectively. Two patients with pretreatment HGT1 had HGT1 recurrences at 9 and 12 months. No patients progressed to T2 disease, underwent radical cystectomy, or had radiographic evidence of metastatic disease. Grade 1 AEs were common (23/25 patients) including hematuria, urinary frequency, urgency, and fatigue. Five patients (20%) experienced a Grade 3 AE including hematuria and UTI.

Limitations

This study was single center and single arm, and included a relatively low proportion of patients with CIS.

Interpretation for Patient Care

This single-arm phase 2 trial demonstrates that intravesical GemDoce was well tolerated with promising efficacy for patients with BCG-naïve high-risk NMIBC. These results provide impetus for conducting a prospective phase 3 trial comparing BCG and GemDoce (BRIDGE) in an analogous patient population.