RT Journal Article
T1 A Randomized Open-Label Phase III Trial Evaluating the Addition of Denosumab to Standard First-Line Treatment in Advanced NSCLC: The European Thoracic Oncology Platform (ETOP) and European Organisation for Research and Treatment of Cancer (EORTC) SPLENDOUR Trial.
A1 Peters, Solange
A1 Danson, Sarah
A1 Hasan, Baktiar
A1 Dafni, Urania
A1 Reinmuth, Niels
A1 Majem, Margarita
A1 Tournoy, Kurt G
A1 Mark, Michael T
A1 Pless, Miklos
A1 Cobo, Manuel
A1 Rodriguez-Abreu, Delvys
A1 Falchero, Lionel
A1 Moran, Teresa
A1 Ortega Granados, Ana Laura
A1 Monnet, Isabelle
A1 Mohorcic, Katja
A1 Sureda, Bartomeu Massutí
A1 Betticher, Daniel
A1 Demedts, Ingel
A1 Macias, Jose Antionio
A1 Cuffe, Sinead
A1 Luciani, Andrea
A1 Sanchez, Jose Garcia
A1 Curioni-Fontecedro, Alessandra
A1 Gautschi, Oliver
A1 Price, Gillian
A1 Coate, Linda
A1 von Moos, Roger
A1 Zielinski, Christoph
A1 Provencio, Mariano
A1 Menis, Jessica
A1 Ruepp, Barbara
A1 Pochesci, Alessia
A1 Roschitzki-Voser, Heidi
A1 Besse, Benjamin
A1 Rabaglio, Manuela
A1 O'Brien, Mary E R
A1 Stahel, Rolf A
K1 Bone metastases
K1 Denosumab
K1 NSCLC
K1 RANK
K1 RANKL
AB Receptor activator of NF-kB ligand stimulates NF-kB-dependent cell signaling and acts as the primary signal for bone resorption. Retrospective analysis of a large trial comparing denosumab versus zoledronic acid in bone metastatic solid tumors suggested significant overall survival (OS) advantage for patients with lung cancer with denosumab (p = 0.01). The randomized open-label phase III SPLENDOUR trial was designed to evaluate whether the addition of denosumab to standard first-line platinum-based doublet chemotherapy improved OS in advanced NSCLC. Patients with stage IV NSCLC were randomized in a 1:1 ratio to either chemotherapy with or without denosumab (120 mg every 3-4 wks), stratified by the presence of bone metastases (at diagnosis), Eastern Cooperative Oncology Group performance status, histology, and region. To detect an OS increase from 9 to 11.25 months (hazard ratio [HR] = 0.80), 847 OS events were required. The trial closed prematurely owing to decreasing accrual rate. A total of 514 patients were randomized, with 509 receiving one or more doses of the assigned treatment (chemotherapy: 252, chemotherapy-denosumab: 257). The median age was 66.1 years, 71% were men, and 59% were former smokers. Bone metastases were identified in 275 patients (53%). Median OS (95% confidence interval [CI]) was 8.7 (7.6-11.0) months in the control arm versus 8.2 (7.5-10.4) months in the chemotherapy-denosumab arm (HR = 0.96; 95% CI: 0.78-1.19; one-sided p = 0.36). For patients with bone metastasis, HR was 1.02 (95% CI: 0.77-1.35), whereas for those without, HR was 0.90 (95% CI: 0.66-1.23). Adverse events grade 3 or greater were observed in 40.9%, 5.2%, 8.7% versus 45.5%, 10.9%, 10.5% of patients. Conditional power for OS benefit was less than or equal to 10%. Denosumab was well-tolerated without unexpected safety concerns. There was no OS improvement for denosumab when added to chemotherapy in the intention-to-treat population and the subgroups with and without bone metastases. Our data do not provide evidence of a clinical benefit for denosumab in patients with NSCLC without bone metastases.
YR 2020
FD 2020-06-18
LK http://hdl.handle.net/10668/15788
UL http://hdl.handle.net/10668/15788
LA en
DS RISalud
RD Apr 11, 2025