On March 28, the U.S. Food and Drug Administration (FDA) approved the PD-L1 inhibitor durvalumab (Imfinzi) with gemcitabine and cisplatin as neoadjuvant treatment, followed by single-agent durvalumab as adjuvant treatment following radical cystectomy, for adults with muscle-invasive bladder cancer.
NIAGARA Trial
Efficacy was evaluated in NIAGARA (ClinicalTrials.gov identifier NCT03732677), a randomized, open-label, multicenter, phase III trial which enrolled 1,063 patients who were candidates for radical cystectomy and had not received prior systemic therapy for bladder cancer. Patients were randomly assigned 1:1 to receive neoadjuvant durvalumab with chemotherapy followed by adjuvant durvalumab after surgery or neoadjuvant chemotherapy followed by surgery alone.
The major efficacy outcome was event-free survival by blinded independent central review; overall survival was an additional efficacy outcome. At a prespecified interim analysis, the trial demonstrated a statistically significant improvement in both event-free and overall survival. Median event-free survival was not reached (95% confidence interval [CI] = not reached to not reached) in the durvalumab with chemotherapy arm and 46.1 months (95% CI = 32.2 months to not reached) in the chemotherapy arm (hazard ratio [HR] = 0.68, 95% CI = 0.56–0.82, two-sided P < .0001). Median overall survival was not reached in either arm (HR = 0.75, 95% CI = 0.59–0.93, two-sided P = .0106).
Adverse reactions were consistent with prior experience with durvalumab with platinum-based chemotherapy.
The recommended durvalumab dose for patients with a body weight of ≥ 30 kg is 1,500 mg every 3 weeks with chemotherapy (neoadjuvant treatment) and 1,500 mg as a single agent every 4 weeks (adjuvant treatment). The recommended durvalumab dose for patients with a body weight < 30 kg is 20 mg/kg with chemotherapy every 3 weeks (neoadjuvant treatment) and 20 mg/kg as a single agent every 4 weeks (adjuvant treatment). Treatment should continue until disease progression that precludes definitive surgery, recurrence, or unacceptable toxicity, or a maximum of eight cycles after surgery.
This review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment. This application was granted Priority Review.
