Research Funding
AstraZeneca
Background
Management of muscle-invasive bladder cancer (MIBC) includes both surgery and systemic therapy. Neoadjuvant cisplatin-based combination chemotherapy has demonstrated improved pathologic complete response (pCR), event-free survival (EFS), and overall survival (OS) compared with radical cystectomy alone. Yet at least half of patients will still experience recurrence and will progress to metastatic disease. Durvalumab (anti–PD-L1 antibody) combined with gemcitabine + cisplatin, administered as either neoadjuvant or adjuvant treatment, may increase the rate of pathologic response and prolong long-term survival. This approach will be evaluated in this study in patients with MIBC identified for curable intent, as reflected in the NCCN guidelines.
Methods
NIAGARA (NCT03732677) is a phase III, randomized, open-label, multicenter, international trial that will enroll ~1050 patients with MIBC who, prior to radical cystectomy, will be randomized (1:1) to durvalumab and gemcitabine + cisplatin (Arm 1) or gemcitabine + cisplatin (Arm 2). Following radical cystectomy, patients in Arm 1 will receive durvalumab monotherapy for 8 cycles (8 months) while patients in Arm 2 will receive no adjuvant treatment. Eligible patients are aged ≥18 years with resectable MIBC (clinical stage T2-T4aN0/1M0) with urothelial histology eligible for a radical cystectomy. Patients with pure non-transitional cell variant histologies and any small cell histology are not eligible. A tumor tissue sample for biomarker analysis is mandatory as PD-L1 expression is a stratification factor. Primary endpoints are pCR and EFS in patients with adequate renal function. Secondary and exploratory endpoints include proportion of patients who achieve pathologic response < stage II (stages Ta, T1, and carcinoma in situ) at the time of cystectomy following neoadjuvant treatment, EFS at 24 months, metastasis-free survival, efficacy of Arm 1 vs Arm 2 at radical cystectomy and proportion of patients who undergo cystectomy, OS rate at 5 years, safety, patient-reported outcomes, and pharmacokinetics. Immunogenicity and biomarkers are exploratory endpoints. Enrollment opened in Dec 2018. Clinical trial information: NCT03732677