PT  - JOURNAL ARTICLE
AU  - Landi, Lorenza
AU  - D’Incà, Federica
AU  - Gelibter, Alain
AU  - Chiari, Rita
AU  - Grossi, Francesco
AU  - Delmonte, Angelo
AU  - Passaro, Antonio
AU  - Signorelli, Diego
AU  - Gelsomino, Francesco
AU  - Galetta, Domenico
AU  - Giannarelli, Diana
AU  - Soto Parra, Hector
AU  - Minuti, Gabriele
AU  - Tiseo, Marcello
AU  - Migliorino, Maria Rita
AU  - Cognetti, Francesco
AU  - Toschi, Luca
AU  - Bidoli, Paolo
AU  - Piantedosi, Francovito
AU  - Calabro’, Luana
AU  - Cappuzzo, Federico
TI  - Bone metastases and immunotherapy in patients with advanced non-small-cell lung cancer
AID  - 10.1186/s40425-019-0793-8
DP  - 2019 Dec 01
TA  - Journal for ImmunoTherapy of Cancer
PG  - 316
VI  - 7
IP  - 1
4099  - http://jitc.bmj.com/content/7/1/316.short
4100  - http://jitc.bmj.com/content/7/1/316.full
SO  - J Immunother Cancer2019 Dec 01; 7
AB  - 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.Abbreviations:AEAdverse eventALKAnaplastic lymphoma kinaseBoMBone metastasesBRAFSerine/threonine-protein kinase B-RafCIConfidence intervalCRComplete responseEAPExpanded Access ProgramECOGEastern Cooperative Oncology GroupEGFREpidermal growth factor receptorHBVHepatitis B virusHCVHepatitis B virusHIVHuman immunodeficiency virusHRHazard ratioICIImmune checkpoint inhibitorKRASKirsten rat sarcoma viral oncogene homologMDSCMyeloid-derived suppressor cellNSCLCNon-small-cell lung cancerNVNot valuableORRObjective response rateOSOverall survivalPDProgressive diseasePD-1Programmed death-1 receptorPD-L1PD-ligand 1PFSProgression free survivalPRPartial responsePSPerformance statusRECISTResponse Evaluation in Solid TumorsROS1c-ros oncogene 1SDStable diseaseTMBTumor Mutational BurdenTRAETreatment related adverse eventUnkUnknownVEGFVascular endothelial growth factor