RT Journal Article
SR Electronic
T1 Bone metastases and immunotherapy in patients with advanced non-small-cell lung cancer
JF Journal for ImmunoTherapy of Cancer
JO J Immunother Cancer
FD BMJ Publishing Group Ltd
SP 316
DO 10.1186/s40425-019-0793-8
VO 7
IS 1
A1 Landi, Lorenza
A1 D’Incà, Federica
A1 Gelibter, Alain
A1 Chiari, Rita
A1 Grossi, Francesco
A1 Delmonte, Angelo
A1 Passaro, Antonio
A1 Signorelli, Diego
A1 Gelsomino, Francesco
A1 Galetta, Domenico
A1 Giannarelli, Diana
A1 Soto Parra, Hector
A1 Minuti, Gabriele
A1 Tiseo, Marcello
A1 Migliorino, Maria Rita
A1 Cognetti, Francesco
A1 Toschi, Luca
A1 Bidoli, Paolo
A1 Piantedosi, Francovito
A1 Calabro’, Luana
A1 Cappuzzo, Federico
YR 2019
UL http://jitc.bmj.com/content/7/1/316.abstract
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