@article{3031559,
    title = "Combined, patient-level, analysis of two randomised trials evaluating
the addition of denosumab to standard first-line chemotherapy in
advanced NSCLC - The ETOP/EORTC SPLENDOUR and AMGEN-249 trials",
    author = "Peters, Solange and Danson, Sarah and Ejedepang, Dunson and Dafni, and Urania and Hasan, Baktiar and Radcliffe, Hoi-Shen and Bustin, Frederique and and Crequit, Jacky and Coate, Linda and Guillot, Monica and Surmont, and Veerle and Rauch, Daniel and Rudzki, Jakob and O'Mahony, Deirdre and and Aranda, Isidoro Barneto and Scherz, Amina and Tsourti, Zoi and and Roschitzki-Voser, Heidi and Pochesci, Alessia and Demonty, Gaston and and Stahel, Rolf A. and O'Brien, Mary",
    journal = "Lung Cancer",
    year = "2021",
    volume = "161",
    pages = "76-85",
    publisher = "Elsevier Ireland Ltd",
    issn = "0169-5002",
    doi = "10.1016/j.lungcan.2021.09.002",
    keywords = "NSCLC; RANKL; DENOSUMAB; BONE METASTASES",
    abstract = "Introduction: The efficacy of adding denosumab to standard first-line
chemotherapy for advanced NSCLC patients has been evaluated in two
separate randomised trials (SPLENDOUR and AMGEN-249). In this pooled
analysis, we will assess the combination-treatment effect in the largest
available population, in order to conclude about the potential impact of
denosumab in NSCLC. Methods: Both trials included in this combined
analysis, were randomised (SPLENDOUR 1:1, AMGEN-249 2:1) multi-centre
trials stratified by histology, bone metastasis, geographical region and
for SPLENDOUR only, ECOG PS. Cox proportional hazards models, were used
to assess the treatment effect with respect to overall survival (OS;
primary endpoint) and progression-free survival (PFS; secondary
endpoint). Heterogeneity between trials was assessed, and subgroup
analyses were performed. Results: The pooled analysis was based on 740
randomised patients (SPLENDOUR:514; AMGEN-249:226), with 407 patients in
the chemotherapy-denosumab arm and 333 in the chemotherapy-alone arm. In
the chemotherapy-denosumab arm, at a median follow-up of 22.0 months,
277 (68.1%) deaths were reported with median OS 9.2 months
(95%CI:[8.0-10.7]), while in the chemotherapy-alone arm, with similar
median follow-up of 20.3 months, 230 (69.1%) deaths with median OS 9.9
months (95%CI:[8.2-11.2]). No significant denosumab effect was found
(HR = 0.98; 95%CI:[0.82-1.18]; P = 0.85). Among subgroups,
interaction was found between treatment and histology subtypes (P =
0.020), with a sta-tistically significant benefit in the squamous group
(HR = 0.70; 95%CI:[0.49-0.98]; P = 0.038), from 7.6 to 9.0 months
median OS. With respect to PFS, 363 (89.2%) and 298 (89.5%) events
were reported in the chemotherapy-denosumab and chemotherapy-alone arms,
respectively, with corresponding medians 4.8 months (95%CI:[4.4-5.3])
and 4.9 months (95%CI:[4.3-5.4]). HR for PFS was 0.97
(95%CI:[0.83-1.15]; P = 0.76), indicating that no significant
denosumab benefit existed for PFS. Conclusion: In this pooled analysis,
no statistically significant improvement was shown in PFS/OS with the
combination of denosumab and chemotherapy for advanced NSCLC and no
meaningful benefit in any of the subgroups."
}