System Maintenance Notice

Please note that maintenance work is scheduled between 4 AM and 5 AM - CET. During this time, you may experience reduced performance. Thanks for your patience.

Publications

Journal Article Epublish

PubMed: 42662853 DOI: 10.1016/j.jbo.2026.100797

Dissociated skeletal response to first-line immunotherapy in synchronous bone metastatic non-small cell lung cancer patients: Clinical profiles and survival benefit of denosumab adjunction.

J Bone Oncol 60:100797

Authors: E Massy, N Stacoffe, M Fauvernier, M Duruisseaux, E Grolleau, M Lamkhioued, M Pérol, C Domblides, M Roche, A Stuani, P Clézardin, E Bonnelye, J B Pialat, N Girard, C Confavreux

Affiliations

  • Département de Rhumatologie Sud, Centre Expert des Métastases Osseuses (CEMOS), Hôpital Lyon Sud, Institut de Cancérologie des Hospices Civils de Lyon, Pierre-Bénite F-69495, France.
  • Centre de Recherche en Cancérologie de Lyon (CRCL) - UMR INSERM 1052 CNRS 5286, Université Claude Bernard Lyon 1, Université de Lyon, Lyon F-69100, France.
  • Service de Radiologie, Hôpital Lyon Sud - Centre Expert des Métastases Osseuses (CEMOS), Hôpital Lyon Sud, Institut de Cancérologie des Hospices Civils de Lyon, Pierre-Bénite F-69495, France.
  • UMR CNRS 5558 LBBE, Université Claude Bernard Lyon 1, Université de Lyon, Lyon F-69100, France.
  • Service de Biostatistiques-Bioinformatique, Pôle de Santé Publique, Hôpital Lyon Sud, Pierre-Bénite F-69495, France.
  • Service de Pneumologie, Hôpital Louis Pradel, Institut de Cancérologie des Hospices Civils de Lyon, Bron F-69500, France.
  • Service de Pneumologie, Hôpital Lyon Sud, Institut de Cancérologie des Hospices Civils de Lyon, Pierre-Bénite F-69495, France.
  • Service de pneumologie, Hôpital de la Croix rousse, Hospices Civils de Lyon, Lyon F-6004, France.
  • Département de Cancérologie Médicale, Centre Léon Bérard, Lyon F-69008, France.
  • Service d'Oncologie, CHU de Bordeaux, F-33000 Bordeaux, France.
  • Plateforme Transversale de Recherche Clinique de l'Institut de Cancérologie, HCL, Pierre-Bénite F-69495, France.
  • LYOS INSERM UMR1033 - Université Claude Bernard Lyon 1, Université de Lyon, Lyon F-69100, France.
  • Canther-cancer heterogeneity, plasticity and resistance to therapies, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, UMR9020-UMR1277, Lille, France.
  • Institut Curie, Department of Medical Oncology, Paris, F-75000 France - Université Paris-Saclay, Université Versailles Saint-Quentin-en-Yvelines, Versailles, F-78000, France.

Abstract

INTRODUCTION

Patients with bone metastases (BM) from non-small cell lung cancer (NSCLC) derive less clinical benefit from immune checkpoint inhibitors (ICIs) than those without skeletal involvement. We aimed to characterize bone-specific disease control profiles under first-line ICI therapy and explore the association of denosumab with clinical outcomes.

METHODS

We conducted a multicenter retrospective study in BM-NSCLC patients, naïve to systemic therapy, treated with first-line ICI monotherapy, with or without denosumab. Radiological response in soft tissue and bone compartments was assessed at 6 months using iRECIST. Disease control (DCR: iCR, iPR, or iSD) and dissociated response (discordant DCR between compartments) were predefined. Denosumab impact was evaluated using logistic regression and Cox models.

RESULTS

Sixty-one patients were included (16 women [26%]; mean age 65.8 ± 9.6 years). Soft tissue DCR was 64% and bone DCR was 62% at M6. Dissociated response occurred in 21% (n = 13), associated with female sex, KRAS mutations, and elevated C-reactive protein (all p < 0.05). Denosumab did not alter bone DCR (73% vs. 60%; adjusted OR 0.64; 95% CI: 0.12-2.99; p = 0.582) but was associated with improved progression-free survival (log-rank p = 0.06) and reduced hazard of progression or death (adjusted HR 0.28; 95% CI: 0.06-1.33; p = 0.110).

CONCLUSION

ICI-driven immune activation does not translate uniformly across compartments. Female sex, KRAS mutation, and systemic inflammation are potential determinants of bone-specific resistance. While denosumab did not significantly modify bone DCR, its trend toward association with improved progression-free survival and reduced risk of progression or death generates the hypothesis of an immunomodulatory effect warranting prospective evaluation.

MeSH

Cells, Lung, Progression-Free Survival, Neoplasms, Carcinoma, Non-Small-Cell Lung, Immunotherapy, Denosumab, Lung Neoplasms, Small Cell Lung Carcinoma, Sex, Therapeutics, Tissues, Mutation