title: Plasma biomarkers correlating with clinical outcome in a phase II study of sorafenib in advanced NSCLC.
abstract: We investigated the relationship between plasma protein biomarker concentrations and clinical outcomes in 52 patients with relapsed/refractory advanced non-small cell lung cancer (NSCLC) treated with 400~mg bid sorafenib in a phase II trial. Blood samples were collected at baseline, on day 15 of cycle 1 (C1D15), and on day 1 of cycle 3 (C3D1), and plasma concentrations of total VEGF, VEGF-165, soluble (s) VEGFR-2, PDGF-BB, sPDGFR-β, sEGFR, sHER-2, uPA, PAI-1, uPAR, TIMP-1, and circulating Ras p21 were assayed by ELISA. Elevated baseline VEGF, VEGF-165, PDGF-BB, Ras p21, and TIMP-1 concentrations were associated with poorer patient outcomes (shorter overall survival [OS] and/or progression-free survival [PFS]). During treatment, the mean concentrations of sVEGFR-2, PDGF-BB, sPDGFR-β, TIMP-1, uPAR, and PAI-1 decreased, while the mean sEGFR concentration increased. Increases in VEGF, VEGF-165, PDGF-BB, and TIMP-1 during treatment were associated with better outcomes (longer OS and/or PFS), whereas increases in plasma Ras p21 during treatment were associated with shorter PFS. The associations between baseline concentrations and/or pharmacodynamic changes in plasma proteins and clinical outcomes in NSCLC patients treated with sorafenib suggest that these biomarkers may have a prognostic role and/or predict the efficacy of sorafenib in patients with NSCLC.
authors: University of Texas, M.D. Anderson Cancer Center, Houston, TX 77030, USA. gblumens@mdanderson.org
authors: George R
authors: GR
authors: Blumenschein
authors: Martin
authors: M
authors: Reck
authors: Frank
authors: F
authors: Fossella
authors: David J
authors: DJ
authors: Stewart
authors: Chetan
authors: C
authors: Lathia
authors: Carol
authors: C
authors: Peña
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001557:Benzenesulfonates / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000097:blood*; D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood* / Q000188:drug therapy / Q000401:mortality / Q000473:pathology; D017322:Clinical Trials, Phase II as Topic; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000097:blood* / Q000188:drug therapy / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009536:Niacinamide / Q000031:analogs & derivatives; D010671:Phenylurea Compounds; D016016:Proportional Hazards Models; D011725:Pyridines / Q000627:therapeutic use*; D000077157:Sorafenib; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D001557:Benzenesulfonates; D014408:Biomarkers, Tumor; D010671:Phenylurea Compounds; D011725:Pyridines; D009536:Niacinamide; D000077157:Sorafenib