Gemcitabine-BCG Shows Early Promise in BCG-Exposed NMIBC
BCG with gemcitabine was linked to strong early oncological efficacy and safety in previously treated patients with non–muscle-invasive bladder cancer.
Gal Wald, MD
Clinical Associate in Urology
Weill Cornell Medical College
Research Fellow
Memorial Sloan Kettering Cancer Center
New York, NY
THE COMBINATION OF BCG and gemcitabine was associated with strong early oncological efficacy and safety in previously treated patients with non–muscle-invasive bladder cancer (NMIBC), according to findings presented at the 25th Annual Meeting of the Society of Urologic Oncology (SUO) in Dallas, Texas.1
The data were presented by Gal Wald, MD, a urology resident at Weill Cornell Medicine and research fellow at Memorial Sloan Kettering Cancer Center, both in New York, New York. “More than half of patients who initially respond to BCG monotherapy [experience] relapse within 5 years. These patients are typically given another course of BCG, but they tend to have even lower response rates,” Wald told Targeted Therapies in Oncology.
“The current standard of care for BCG-exposed NMIBC is retreatment with BCG alone, but only 50% will have clinical benefit,” the authors wrote. “Combination strategies that can enhance the effectiveness of BCG to prevent BCG-unresponsive disease are needed.”
Reviewing the current armamentarium of BCG-based combination treatments, Wald pointed to high costs as well as toxicity in the case of many of the agents. Wald also discussed mitomycin vs intravesical gemcitabine, pointing to findings from 2 studies attesting to greater efficacy and tolerability with the latter.2,3 Comparing BCG with gemcitabine, Wald cited research that the latter is more effective in the BCG-refractory space.4
For the current study, the authors hypothesized that the combination of gemcitabine and BCG “will have improved response rates compared [with] historic outcomes with retreatment with BCG alone.” The primary end point was complete response (CR) at 6 months, defined as “proportion of patients who are disease free within the bladder by cystoscopy (with or without biopsy) and urinary cytology.”
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The study had a 2-stage design, with 15 patients accrued for the first stage and 28 additional patients for the second stage. Patients were eligible for inclusion if they had pathologic high-grade (HG) Ta, HG T1, and/or T1 disease; were within 24 months of prior BCG exposure; had an absence of urothelial carcinoma involving the upper urinary tract within 12 months from start of treatment; were at least 18 years old; and had a Karnofsky performance status of at least 60%. Patients with current BCG-unresponsive NMIBC, current evidence of concurrent extravesical (urethra, ureter, or renal pelvis) urothelial cell carcinoma, a history of muscle-invasive (stage ≥ T2) or metastatic urothelial cell carcinoma, or a contraindication to BCG were excluded from the study.
The treatment regimen consisted of gemcitabine 2000 mg twice weekly and TICE BCG strain 50 mg weekly. Patients who did not have high-grade recurrence were continued on SWOG maintenance BCG. At trial entry, histology was as follows:
• Carcinoma in situ (CIS) only: 21 patients (49%)
• Ta plus CIS: 10 patients (23%)
• T1 plus CIS: 1 patient (2.3%)
• Ta only: 8 patients (19%)
• T1 only: 3 patients (7%)
In terms of prior treatments, median total number of prior BCG instillations was 6 (range, 5-24), 5 patients (12%) had received prior maintenance BCG, and 5 patients (12%) had received at least 2 induction courses. In addition, median time since last BCG was 6 months (IQR, 4-15). In terms of other intravesical regimens, 2 patients (4.7%) received induction gemcitabine, 2 patients (4.7%) received gemcitabine plus docetaxel, and 1 patient (2.3%) received BCG plus interferon.
CR rate was 98% (n = 39 of 40) at 3 months, 94% at 6 months (n = 34 of 36), and 81% at 12 months (n = 21 of 26). In the CIS plus or minus papillary disease cohort, the CR rate was 100% at 3 months (n = 31), 97% at 6 months (n = 28 of 29), and 80% at 12 months (n = 16 of 20).
HG recurrence-free survival was 97% at 6 months, 85% at 12 months, and 76% at 18 months. In addition, 12-month cystectomy-free survival was 100% (n = 26).
Regarding treatment-related adverse events (TRAEs), 2 patients (5%) experienced a grade 3 TRAE. One was urinary tract infection, and the other was BCG-related pneumonitis. No grade 4/5 toxicity was observed.
Wald said that based on the findings of the study presented at SUO 2024, a phase 3 randomized trial, GAIN (NCT05024734), will be opening in May 2025. “Our study does demonstrate excellent early oncological efficacy, but it does represent a relatively small cohort of 43 patients,” Wald said. “The data are yet to mature, so we don’t think the early results of [this] phase 2 [trial] should be practice changing right now. We have to wait until our data fully mature and we see the results from a phase 3 trial.”
