Journal article
Evaluation of KRAS Mutations, Angiogenic Biomarkers, and DCE-MRI in Patients with Advanced Non-Small-Cell Lung Cancer Receiving Sorafenib
Clinical cancer research, Vol.17(5), pp.1190-1199
01 Mar 2011
PMID: 21224376
Featured in Collection : UN Sustainable Development Goals @ Drexel
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. Clin Cancer Res; 17(5); 1190-9. (c) 2011 AACR.
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Details
- Title
- Evaluation of KRAS Mutations, Angiogenic Biomarkers, and DCE-MRI in Patients with Advanced Non-Small-Cell Lung Cancer Receiving Sorafenib
- Creators
- Ronan J. Kelly - National Institutes of Health Clinical CenterArun Rajan - Center for Cancer ResearchJeremy Force - Center for Cancer ResearchAriel Lopez-Chavez - National Institutes of Health Clinical CenterCorrine Keen - Center for Cancer ResearchLiang Cao - Center for Cancer ResearchYunkai Yu - National Cancer InstitutePeter Choyke - Center for Cancer ResearchBaris Turkbey - Center for Cancer ResearchMark Raffeld - Center for Cancer ResearchLiqiang Xi - Center for Cancer ResearchSeth M. Steinberg - National Cancer InstituteJohn J. Wright - NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USAShivaani Kummar - Center for Cancer ResearchMartin Gutierrez - National Cancer InstituteGiuseppe Giaccone - Center for Cancer Research
- Publication Details
- Clinical cancer research, Vol.17(5), pp.1190-1199
- Publisher
- Amer Assoc Cancer Research
- Number of pages
- 10
- Grant note
- NIH, NCI, Center for Cancer Research; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) NCI, NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- General Internal Medicine
- Web of Science ID
- WOS:000287914400026
- Scopus ID
- 2-s2.0-79952269551
- Other Identifier
- 991022060043204721
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