Gemcitabine plus docetaxel may be a feasible alternative to first-line BCG in NMIBC

Patients received either sequential intravesical gemcitabine (1 g) and docetaxel (37.5 mg) or 1 vial of BCG.

Combination therapy of sequential intravesical gemcitabine and docetaxel was associated with less high-grade disease recurrence and treatment discontinuation compared with treatment with bacillus Calmette-Guérin (BCG) therapy in patients with non–muscle-invasive bladder cancer (NMIBC), according to findings presented in JAMA Network.¹

These data indicate that gemcitabine and docetaxel could serve as a feasible alternative for patients with high-risk NMIBC during the continued BCG shortage.

The retrospective study included 312 patients with high-risk treatment-naïve NMIBC. From the cohort, 174 patients were treated with the standard of care BCG therapy and 138 were treated with gemcitabine and docetaxel therapy.

Patients received either sequential intravesical gemcitabine (1 g) and docetaxel (37.5 mg) or 1 vial of BCG. Induction regimens were administered to patients once per week for 6 weeks, and maintenance regimens were given if the patient was disease-free at the time of first follow-up. The median follow-up time was 49 months for the BCG group and 23 months for the gemcitabine and docetaxel group.

Investigators considered patients’ tolerance to therapy and oncological outcomes in their analysis. The primary end point was high-grade recurrence free-survival (RFS). Secondary outcome measures included progression free survival (PFS), cystectomy-free survival (CFS), cancer-specific survival (CSS), and overall survival (OS).

After controlling for age, sex, treatment year, and presence of carcinoma in situ, the investigators found that treatment with gemcitabine and docetaxel was associated with improved high-grade RFS (P = .04) and RFS (P = .02) compared with treatment with BCG.

At 6 months, high-grade RFS in the BCG group was 76%, compared with 92% in the gemcitabine and docetaxel group. At 2 years, high-grade RFS in the BCG group was 69% compared with 81% in the gemcitabine and docetaxel group. In the BCG group, 69 patients experienced recurrence and 60 experienced high-grade recurrence, and in the gemcitabine and docetaxel group, 32 patients experienced recurrence and 28 experienced high-grade recurrence.

The secondary outcome measure of PFS showed a rate of 92% in the BCG group compared with 97% in the gemcitabine and docetaxel group. Rates of CFS were 94% in the BCG group and 98% in the gemcitabine and docetaxel group. CSS rates were 98% in the BCG group and 100% for the gemcitabine and docetaxel group. Rates of OS were 93% in the BCG group and 89% for the gemcitabine and docetaxel group.

Induction treatment discontinuation rates due to adverse events (AEs) were also improved in the gemcitabine and docetaxel group (2.9%) compared with the BCG group (9.2%) (P = .02). In the BCG group, 86 patients (49.4%) reported experiencing AEs compared with 72 patients (52.2%) in the gemcitabine and docetaxel group. Grade 3 to 5 AEs were experienced in 7 patients (4.0%) from the BCG group and 2 patients (1.4%) from the gemcitabine and docetaxel group.

These findings indicate the feasibility of sequential intravesical gemcitabine plus docetaxel as an alternative first-line treatment for BCG-naïve NMIBC. The data also provide support for the phase 3 BRIDGE trial (NCT05538663),² which will compare event-free survival for BCG vs gemcitabine plus docetaxel in patients with BCG-naïve NMIBC. The BRIDGE study is currently recruiting participants.

References

1. McElree IM, Steinberg RL, Mott SL, O’Donnell MA, Packiam VT. Comparison of sequential intravesical gemcitabine and docetaxel vs Bacillus Calmette-Guérin for the treatment of patients with high-risk non-muscle–invasive bladder cancer. JAMA Network. 2023;6(2):e230849. doi:10.1001/jamanetworkopen.2023.0849.

2. Intravesical BCG vs GEMDOCE in NMIBC (BRIDGE). ClinicalTrials.gov. Updated January 13, 2023. Accessed March 1, 2023. https://clinicaltrials.gov/ct2/show/study/NCT05538663