Bone metastases and immunotherapy in patients with advanced non-small-cell lung cancer

Lorenza Landi, Federica D'Incà, Alain Gelibter, Rita Chiari, Francesco Grossi, Angelo Delmonte, Antonio Passaro, Diego Signorelli, Francesco Gelsomino, Domenico Galetta, Diana Giannarelli, Hector Soto Parra, Gabriele Minuti, Marcello Tiseo, Maria Rita Migliorino, Francesco Cognetti, Luca Toschi, Paolo Bidoli, Francovito Piantedosi, Luana Calabro'Federico Cappuzzo

Research output: Contribution to journalArticlepeer-review


BACKGROUND: Bone metastases (BoM) are a negative prognostic factor in non-small-cell lung cancer (NSCLC). Beyond its supportive role, bone is a hematopoietic organ actively regulating immune system. We hypothesized that BoM may influence sensitivity to immunotherapy. METHODS: Pretreated non-squamous (cohort A) and squamous (cohort B) NSCLCs included in the Italian Expanded Access Program were evaluated for nivolumab efficacy according to BoM. RESULTS: Cohort A accounted for 1588 patients with non-squamous NSCLC, including 626 (39%) with (BoM+) and 962 (61%) without BoM (BoM-). Cohort B accounted for 371 patients with squamous histology including 120 BoM+ (32%) and 251 (68%) BoM- cases. BoM+ had lower overall response rate (ORR; Cohort A: 12% versus 23%, p <  0.0001; Cohort B: 13% versus 22%, p = 0.04), shorter progression free survival (PFS; Cohort A: 3.0 versus 4.0 months, p <  0.0001; Cohort B: 2.7 versus 5.2 months, p <  0.0001) and overall survival (OS; Cohort A: 7.4 versus 15.3 months, p <  0.0001; Cohort B: 5.0 versus 10.9 months, p < 0.0001). Moreover, BoM negatively affected outcome irrespective of performance status (PS; OS in both cohorts: p < 0.0001) and liver metastases (OS cohort A: p < 0.0001; OS Cohort B: p = 0.48). At multivariate analysis, BoM independently associated with higher risk of death (cohort A: HR 1.50; cohort B: HR 1.78). CONCLUSIONS: BoM impairs immunotherapy efficacy. Accurate bone staging should be included in clinical trials with immunotherapy.

Original languageEnglish
Article number316
JournalJournal for ImmunoTherapy of Cancer
Issue number1
Publication statusPublished - Nov 21 2019


  • Bone metastases
  • Immunotherapy
  • Nivolumab
  • Non-small-cell lung cancer
  • PD-L1

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Molecular Medicine
  • Oncology
  • Pharmacology
  • Cancer Research


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