title: Systemic inflammatory status at baseline predicts bevacizumab benefit in advanced non-small cell lung cancer patients.
abstract: Bevacizumab is a humanized anti-VEGF monoclonal antibody able to produce clinical benefit in advanced non-squamous non-small-cell lung cancer (NSCLC) patients when combined to chemotherapy. At present, while there is a rising attention to bevacizumab-related adverse events and costs, no clinical or biological markers have been identified and validated for baseline patient selection. Preclinical findings suggest an important role for myeloid-derived inflammatory cells, such as neutrophils and monocytes, in the development of VEGF-independent angiogenesis. We conducted a retrospective analysis to investigate the role of peripheral blood cells count and of an inflammatory index, the neutrophil-to-lymphocyte ratio (NLR), as predictors of clinical outcome in NSCLC patients treated with bevacizumab plus chemotherapy. One hundred and twelve NSCLC patients treated with chemotherapy ± bevacizumab were retrospectively evaluated for the predictive value of clinical or laboratory parameters correlated with inflammatory status. Univariate analysis revealed that a high number of circulating neutrophils and monocytes as well as a high NLR were associated with shorter progression-free survival (PFS) and overall survival (OS) in bevacizumab-treated patients only. We have thus developed a model based on the absence or the presence of at least one of the above-mentioned inflammatory parameters. We found that the absence of all variables strongly correlated with longer PFS and OS (9.0 vs. 7.0 mo, HR: 0.39, p = 0.002; and 20.0 vs. 12.0 mo, HR: 0.29, p < 0.001 respectively) only in NSCLC patients treated with bevacizumab plus chemotherapy. Our results suggest that a baseline systemic inflammatory status is marker of resistance to bevacizumab treatment in NSCLC patients.
authors.affiliation: Medical Oncology Unit, Campus Salvatore Venuta, Department of Experimental and Clinical Medicine, Magna Graecia University and Tommaso Campanella Cancer Center, Catanzaro, Italy.
authors.forename: Cirino
authors.initials: C
authors.lastname: Botta
authors.forename: Vito
authors.initials: V
authors.lastname: Barbieri
authors.forename: Domenico
authors.initials: D
authors.lastname: Ciliberto
authors.forename: Antonio
authors.initials: A
authors.lastname: Rossi
authors.forename: Danilo
authors.initials: D
authors.lastname: Rocco
authors.forename: Raffaele
authors.initials: R
authors.lastname: Addeo
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Staropoli
authors.forename: Pierpaolo
authors.initials: P
authors.lastname: Pastina
authors.forename: Giulia
authors.initials: G
authors.lastname: Marvaso
authors.forename: Ignazio
authors.initials: I
authors.lastname: Martellucci
authors.forename: Annamaria
authors.initials: A
authors.lastname: Guglielmo
authors.forename: Luigi
authors.initials: L
authors.lastname: Pirtoli
authors.forename: Pasquale
authors.initials: P
authors.lastname: Sperlongano
authors.forename: Cesare
authors.initials: C
authors.lastname: Gridelli
authors.forename: Michele
authors.initials: M
authors.lastname: Caraglia
authors.forename: Pierfrancesco
authors.initials: P
authors.lastname: Tassone
authors.forename: Pierosandro
authors.initials: P
authors.lastname: Tagliaferri
authors.forename: Pierpaolo
authors.initials: P
authors.lastname: Correale
mesh_terms: D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068258:Bevacizumab; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality / Q000473:pathology; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009367:Neoplasm Staging; D009504:Neutrophils / Q000276:immunology; D010976:Platelet Count; D017671:Platinum Compounds / Q000008:administration & dosage; D012189:Retrospective Studies; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D017671:Platinum Compounds; D000068258:Bevacizumab
keywords: angiogenesis; bevacizumab; inflammation; lung cancer; monocytes; neutrophil-to-lymphocyte ratio; neutrophils