TY - JOUR
T1 - Plasma biomarkers correlating with clinical outcome in a phase II study of sorafenib in advanced NSCLC
AU - Blumenschein, George R.
AU - Reck, Martin
AU - Fossella, Frank
AU - Stewart, David J.
AU - Lathia, Chetan
AU - Peña, Carol
N1 - Copyright:
Copyright 2013 Elsevier B.V., All rights reserved.
PY - 2011
Y1 - 2011
N2 - 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.
AB - 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.
KW - Biomarkers
KW - multikinase inhibitor
KW - nonsmall cell lung cancer
KW - sorafenib
KW - targeted treatment
UR - http://www.scopus.com/inward/record.url?scp=84864439956&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84864439956&partnerID=8YFLogxK
U2 - 10.3233/CBM-2012-0253
DO - 10.3233/CBM-2012-0253
M3 - Article
C2 - 22820084
AN - SCOPUS:84864439956
SN - 1574-0153
VL - 10
SP - 287
EP - 298
JO - Cancer Biomarkers
JF - Cancer Biomarkers
IS - 6
ER -