Bone metastases and immunotherapy in patients with advanced non-small-cell lung cancer.
Adult
Aged
Aged, 80 and over
Antineoplastic Agents, Immunological
/ administration & dosage
Biomarkers, Tumor
Bone Neoplasms
/ diagnosis
Carcinoma, Non-Small-Cell Lung
/ drug therapy
Clinical Trials as Topic
Cohort Studies
Female
Humans
Lung Neoplasms
/ drug therapy
Male
Middle Aged
Molecular Targeted Therapy
/ methods
Prognosis
Treatment Outcome
Bone metastases
Immunotherapy
Nivolumab
Non-small-cell lung cancer
PD-L1
Journal
Journal for immunotherapy of cancer
ISSN: 2051-1426
Titre abrégé: J Immunother Cancer
Pays: England
ID NLM: 101620585
Informations de publication
Date de publication:
21 11 2019
21 11 2019
Historique:
received:
13
05
2019
accepted:
30
10
2019
entrez:
23
11
2019
pubmed:
23
11
2019
medline:
22
7
2020
Statut:
epublish
Résumé
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. 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. 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). BoM impairs immunotherapy efficacy. Accurate bone staging should be included in clinical trials with immunotherapy.
Sections du résumé
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.
Identifiants
pubmed: 31752994
doi: 10.1186/s40425-019-0793-8
pii: 10.1186/s40425-019-0793-8
pmc: PMC6868703
doi:
Substances chimiques
Antineoplastic Agents, Immunological
0
Biomarkers, Tumor
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
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