The study enrolled patients with BCG-unresponsive disease, which included those with persistent carcinoma in situ (CIS), or high-grade Ta/T1 tumors at six months despite receiving adequate BCG therapy, patients who have recurrences of high-grade Ta/T1 NMIBC within six months, carcinoma in situ within 12 months of disease-free state after BCG. All patients received 75 mL nadofaragene firadenovec by intravesical administration through a urinary catheter. Repeat administration at months 3, 6, and 9 was done in the absence of high-grade recurrence. The primary endpoint was a 12-month complete response rate defined by negative urine cytology and cystoscopy as assessed by the treating physician.
After excluding patients who did not meet the BCG-unresponsive definition, a total of 151 patients were included in the efficacy analyses with a median age of 71 years. 103 patients had CIS with or without Ta/T1, and 48 patients had high-grade Ta/T1 disease.
In the per-protocol efficacy analysis cohort of CIS patients (with or without a high-grade Ta or T1 tumor) cohort, 55/103 (53.4%) patients achieved a complete response at three months which was significantly higher than the prespecified null hypothesis rate of no more than 27% (p<0·0001). The median duration of response was approximately ten months. 25/103 (24.3%) remained recurrence-free at 12 months. The most common adverse effects were micturition urgency, and there were no treatment-related deaths.
A head-to-head comparison between nadofaragene firadenovec and pembrolizumab or other second-line chemotherapy combinations such gemcitabine-docetaxel is lacking. The cost-effectiveness of these approaches also needs to be considered.
Written by: Bishoy M. Faltas, MD, Director of Bladder Cancer Research, Englander Institute for Precision Medicine, Weill Cornell Medicine, New York City, New York
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