Evaluation of KRAS mutations, angiogenic biomarkers, and DCE-MRI in patients with advanced non-small-cell lung cancer receiving sorafenib. Academic Article uri icon

Overview

abstract

  • PURPOSE: Sorafenib, a multikinase inhibitor targeting Raf and VEGFR, has shown activity in unselected patients with non-small-cell lung cancer (NSCLC). At present there are no validated biomarkers indicative of sorafenib activity. EXPERIMENTAL DESIGN: Patients received sorafenib 400 mg BID daily to determine activity and tolerability and to measure its biological effects. KRAS mutation status (N = 34), angiogenesis markers (VEGF, bFGF, FLT-1, PLGF-1) and imaging with DCE-MRI (dynamic contrast enhanced MRI) to determine early changes in tumor vascular characteristics were evaluated. Three parameters K(trans), K(ep), and V(e) were measured by DCE-MRI at baseline and day 14 of cycle 1. Cytokine analysis was done on days 0, 14, 28, and 54. RESULTS: Thirty-seven patients with previously treated stage IV NSCLC were enrolled in this single-center phase II trial. In 34 evaluable patients, 2 had partial responses and 20 had stable disease for 3 to 17 months, a disease control rate of 65%. The median progression-free survival (PFS) was 3.4 months, and median overall survival (OS) was 11.6 months. Toxicity was consistent with the known side effects of sorafenib. KRAS (32%) and EGFR mutations (22%) showed no correlation with response, PFS, or OS. K(ep), was significant in predicting an improvement in OS (P = 0.035) and PFS (P = 0.029). Cytokine analysis demonstrated an improved OS for bFGF day 0 (<6 vs. >6 pg/mL; P = 0.042), whereas a PFS benefit was seen with bFGF at day 28 (<6 vs. >6; P = 0.028). CONCLUSIONS: KRAS and EGFR mutational status showed no correlation with response, PFS, or OS. Radiologic and cytokine changes may act as biomarkers indicative of early angiogenesis inhibition.

publication date

  • January 11, 2011

Research

keywords

  • Antineoplastic Agents
  • Benzenesulfonates
  • Biomarkers, Tumor
  • Carcinoma, Non-Small-Cell Lung
  • Genes, ras
  • Lung Neoplasms
  • Proto-Oncogene Proteins
  • Pyridines
  • ras Proteins

Identity

PubMed Central ID

  • PMC3048919

Scopus Document Identifier

  • 79952269551

Digital Object Identifier (DOI)

  • 10.1158/1078-0432.CCR-10-2331

PubMed ID

  • 21224376

Additional Document Info

volume

  • 17

issue

  • 5