Phase 2 Trial of Intravesical Gemcitabine and Docetaxel as First-Line Treatment of Bacillus Calmette-Guérin‒Naïve Nonmuscle-Invasive Urothelial Carcinoma: Updated, 3-Year Outcomes.

PURPOSE: Combination intravesical gemcitabine-docetaxel (Gem/Doce) has demonstrated efficacy in bacillus Calmette-Guérin (BCG)‒unresponsive high-risk (HR) nonmuscle-invasive bladder cancer (NMIBC). However, its efficacy as first-line treatment for BCG-naïve HR NMIBC is unknown. We previously reported recurrence-free survival (RFS) at 1 year. In this article, we present updated 3-year outcomes.

MATERIALS AND

METHODS

This study is a prospective, single-arm, open-label phase 2 trial for patients with BCG-naïve HR NMIBC. Intravesical Gem/Doce was given weekly for 6 weeks as induction, followed by monthly maintenance therapy for 2 years. We previously reported the primary end point of 3-month complete response, and here, we present secondary end points of 24-month and 36-month high-grade (HG) RFS, along with updated adverse events (AEs).

RESULTS

Twenty-five patients were enrolled between August 2020 and August 2022 and followed for a median of 50 months with a minimum of 41-month follow-up in all patients with continued response. The cohort included 16 patients (64%) with HGT1, 8 (32%) with HGTa, and 9 (36%) with carcinoma in situ present. High-grade RFS was 84% at 24 months (21/25; 95% CI, 63%-94%) and 80% at 36 months (20/25; 95% CI, 58%-91%). Recurrences occurred at 11, 11, 15, 20, 36, 49, and 65 months post induction. Six of the 7 patients who had HG recurrence were treated with BCG, and 3 have no evidence of disease to date. No patients had progression during Gem/Doce, and 2 patients (8%) underwent cystectomy: one for recurrence during BCG and another for recurrence after a third-line bladder preservation approach. Two patients had low-grade recurrence. Grade 1 AEs occurred in 21 patients (84%), commonly from pain, fatigue, and hematuria. Five patients (20%) experienced a grade 3 AE including hematuria and UTI.

CONCLUSIONS

The updated 3-year results of this single-arm phase 2 trial suggest continued efficacy and durability of Gem/Doce for this small cohort of BCG-naïve HR NMIBC patients.