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Poster Discussion session - NSCLC, metastatic 2

1767 - A randomised phase III trial evaluating the addition of denosumab to standard first-line treatment in advanced NSCLC – the ETOP and EORTC SPLENDOUR trial.


21 Oct 2018


Poster Discussion session - NSCLC, metastatic 2


Supportive Care and Symptom Management;  Therapy

Tumour Site


Solange Peters


Annals of Oncology (2018) 29 (suppl_8): viii493-viii547. 10.1093/annonc/mdy292


S. Peters1, S.J. Danson2, B. Hasan3, N. Reinmuth4, M. Majem5, K.G. Tournoy6, M.T. Mark7, M. Pless8, M. Cobo9, D. Rodriguez-Abreu10, L. Falchero11, B. Massutí12, L. Coate13, R. von Moos14, C.C. Zielinski15, E. De Maio16, M. O'Brien17, H. Roschitzki-Voser18, U. Dafni19, R.A. Stahel20

Author affiliations

  • 1 Département D'oncologie, Centre Hospitalier Universitaire Vaudois (CHUV), 1011 - Lausanne/CH
  • 2 University Of Sheffield, Weston Park Hospital, Sheffield/GB
  • 3 European Organisation For Research And Treatment Of Cancer (eortc), Headquarters, 1200 - Brussels/BE
  • 4 Asklepios Kliniken Gmbh, Asklepios Fachkliniken Muenchen-Gauting, Gauting/DE
  • 5 Medical Oncology Department, Hospital De La Santa Creu I Sant Pau, Barcelona/ES
  • 6 Onze-lieve-vrouw Ziekenhuis (olv) Aalst And, Faculty of Medicine and Life Sciences, Ghent University, Ghent/BE
  • 7 Medical Oncology, Kantonsspital Graubünden, 8000 - Chur/CH
  • 8 Medical Oncology And Hematology, Kantonsspital Winterthur, 8401 - Winterthur/CH
  • 9 Oncología Médica, Hospital Regional Universitario Carlos Haya, Málaga/ES
  • 10 Servicio Oncología Médica, Hospital Insular De Gran Canaria, Las Palmas/ES
  • 11 Medical Oncology, Hopital Nord-Ouest Villefranche, Gleizé/FR
  • 12 Spanish Lung Cancer Group (slcg) And, Hospital Universitario Alicante - ISABIAL Oncologia Médica, Alicante/ES
  • 13 Cancer Trials Ireland And, University Hospital Limerick, Limerick/IE
  • 14 Swiss Group For Clinical Cancer Research (sakk) And, Kantonsspital Graubünden, 8000 - Chur/CH
  • 15 Central European Cooperative Oncology Group (cecog), Comprehensive Cancer Center, Medical University, 1090 - Vienna/AT
  • 16 European Organisation For Research And Treatment Of Cancer (eortc), Headquarters, Brussels/BE
  • 17 Medical Oncology, Royal Marsden Hospital, Sutton/GB
  • 18 European Thoracic Oncology Platform (etop), Coordinating Office, 3008 - Bern/CH
  • 19 Frontier Science Foundation-hellas And, National and Kapodistrian University of Athens, 115 27 - Athens/GR
  • 20 Department Of Haematology And Oncology, Division Of Oncology, University Hospital Zürich, 8091 - Zurich/CH


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Abstract 1767


RANKL stimulates NF-kB-dependent cell signalling and is known to act as primary signal for bone resorption. In a large trial comparing denosumab vs zoledronic acid in bone metastatic solid tumours, retrospective analysis suggested a significant overall survival (OS) advantage in lung cancer patients who were receiving denosumab. SPLENDOUR is a randomised phase III trial, evaluating whether the addition of denosumab to standard first-line platinum-based doublet chemotherapy improves OS in advanced NSCLC.


Stage IV NSCLC patients randomised to the control arm received 4-6 cycles of standard chemotherapy plus best supportive care, if there were no bone metastases, or zoledronic acid in case of skeletal involvement. Patients in the denosumab arm were given standard chemotherapy plus denosumab, 120 mg every 3-4 weeks. Randomisation was stratified by bone metastases, PS, histology and region. 847 OS events were required to detect an OS increase from 9 to 11.25 months (HR = 0.80). The trial closed early due to a decrease in accrual rate.


Total of 514 patients were randomised, with 509 (252 vs 257) patients receiving at least one dose of assigned treatment. Median age was 65.4 vs 66.5 years, the majority were male (73 vs 69%) and former smokers (58 vs 60%). 275 (54 vs 53%) patients had bone metastasis. Median follow-up time with respect to OS was 18.8 vs 25.3 months. Grade 3/4/5 adverse events were observed in 40.9%/5.2%/8.7% vs 45.5%/10.9%/10.5% of patients. Median OS (95% CI) was 8.8 (7.6, 11.0) months in the control vs 8.2 (7.4, 10.4) months in the denosumab arm, HR = 0.96 (95%CI: 0.78-1.19; p = 0.71). Conditional power calculations indicated that if the trial had proceeded to completion, the power of detecting a significant OS benefit would still be less than 10%.


Denosumab was well tolerated without major safety concerns. The final analysis of SPLENDOUR did not show an improvement of OS for denosumab when added to standard first-line platinum-based chemotherapy. These results are at variance with our trial assumption and previous studies. In addition to the primary OS analysis, outcome by subgroups with or without bone metastases will be presented.

Clinical trial identification


Legal entity responsible for the study

European Thoracic Oncology Platform (ETOP).



Editorial Acknowledgement


S.J. Danson: Teaching honoraria to institution: Amgen. Institution has also run multiple trials sponsored by Amgen. N. Reinmuth: Honoraria, speaker and advisory services: Roche, Lilly, Novartis, MSD, BMS, Boehringer-Ingelheim, Astra-Zeneca, Pfizer. B. Massutí: Consulting or advisory role: Roche, Boehringer Ingelheim, BMS, MSD, AstraZeneca; Speaker's bureau: Roche, Amgen, Merck Serono, Pfizer, AstraZeneca, Boehringer Ingelheim; Travel grants: MSD, Janssen, Roche. L. Coate: Travel grants: Amgen, Roche, Pfizer, AstraZeneca, Boehringer Ingleheim; Advisory board: MSD, AstraZeneca,, Pfizer, BI, BMS; Investigator: MSD, BMS, Pfizer sponsored studies. R. von Moos: Advisory board payment to institution: Amgen. All other authors have declared no conflicts of interest.

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