Bone metastases and immunotherapy in patients with advanced non-small-cell lung cancer: Journal for ImmunoTherapy of Cancer

L. Landi, F. D'Incà, A. Gelibter, R. Chiari, F. Grossi, A. Delmonte, A. Passaro, D. Signorelli, F. Gelsomino, D. Galetta, D. Giannarelli, H. Soto Parra, G. Minuti, M. Tiseo, M.R. Migliorino, F. Cognetti, L. Toschi, P. Bidoli, F. Piantedosi, L. Calabro'F. Cappuzzo

Research output: Contribution to journalArticlepeer-review

Abstract

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. © 2019 The Author(s).
Original languageEnglish
JournalJ. Immunother. Cancer
Volume7
Issue number1
DOIs
Publication statusPublished - 2019

Keywords

  • Bone metastases
  • Immunotherapy
  • Nivolumab
  • Non-small-cell lung cancer
  • PD-L1
  • nivolumab
  • adult
  • advanced cancer
  • aged
  • anemia
  • Article
  • asthenia
  • bone metastasis
  • cancer immunotherapy
  • cancer mortality
  • cancer patient
  • cohort analysis
  • controlled clinical trial
  • controlled study
  • drug withdrawal
  • dyspnea
  • fatigue
  • female
  • high risk patient
  • human
  • human tissue
  • liver metastasis
  • major clinical study
  • male
  • multicenter study
  • open study
  • overall survival
  • pneumonia
  • premedication
  • priority journal
  • progression free survival
  • prospective study
  • single drug dose
  • squamous cell lung carcinoma
  • tissue section
  • very elderly

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