A phase III, randomized, open-label, multicenter, global study of efficacy and safety of durvalumab in combination with gemcitabine plus cisplatin for neoadjuvant treatment followed by durvalumab alone for adjuvant treatment in muscle-invasive bladder cancer (NIAGARA)
| Autor: | Stephan Hois, Feng Xiao, Sarah E. Donegan, Hiroyuki Nishiyama, Matthew D. Galsky, Erik T. Goluboff, Joshua J. Meeks, Hikmat Al-Ahmadie, Vanessa Williams, Michiel S. van der Heijden, James W.F. Catto, Thomas Powles |
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| Rok vydání: | 2021 |
| Předmět: |
Cisplatin
Oncology Cancer Research medicine.medical_specialty Durvalumab Bladder cancer business.industry medicine.medical_treatment Muscle invasive Combination chemotherapy medicine.disease Gemcitabine 03 medical and health sciences 0302 clinical medicine Neoadjuvant treatment 030220 oncology & carcinogenesis Internal medicine medicine business Adjuvant 030215 immunology medicine.drug |
| Zdroj: | Journal of Clinical Oncology. 39:TPS505-TPS505 |
| ISSN: | 1527-7755 0732-183X |
| DOI: | 10.1200/jco.2021.39.6_suppl.tps505 |
| Popis: | TPS505 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. |
| Databáze: | OpenAIRE |
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