Plasma biomarkers correlating with clinical outcome in a phase II study of sorafenib in advanced NSCLC

Article type: Research Article

Authors: Blumenschein, Jr., George R.^{a; *} | Reck, Martin^b | Fossella, Frank^a | Stewart, David J.^a | Lathia, Chetan^c | Peña, Carol^c

Affiliations: [a] University of Texas, M.D. Anderson Cancer Center, Houston, TX, USA | [b] Thoracic Oncology, Hospital Grosshansdorf, Grosshansdorf, Germany | [c] Bayer HealthCare Pharmaceuticals, Montville, NJ, USA

Correspondence: [*] Corresponding author: George R. Blumenschein, Jr., MD, M.D. Anderson Cancer Center, 1515 Holcombe Blvd, Box 432, Houston, TX 77030-4009, USA. Tel.: +1 713 792 6363; Fax: +1 713 796 8655; E-mail: gblumens@mdanderson.org.

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.

Keywords: Biomarkers, multikinase inhibitor, nonsmall cell lung cancer, sorafenib, targeted treatment

DOI: 10.3233/CBM-2012-0253

Journal: Cancer Biomarkers, vol. 10, no. 6, pp. 287-298, 2012