Analysis of serum protein levels of angiogenic factors and their soluble receptors as markers of response to cediranib in the NCIC CTG BR.24 clinical trial

作者：Addison Christina L^*; Ding Keyue; Seymour Lesley; Zhao Huijun; Laurie Scott A; Shepherd Frances A; Goss Glenwood D; Bradbury Penelope A

来源：Lung Cancer, 2015, 90(2): 288-295.

DOI：10.1016/j.lungcan.2015.09.004

• Cediranib
• Non-small cell lung cancer
• Biomarker
• VEGF
• sVEGFR
• Prognostic
• Predictive
• Survival

Objectives: Prognostic and predictive ability of circulating vascular endothelial growth factor (VEGF), stromal derived factor (SDF)-1 alpha and soluble VEGF receptors (sVEGFR) 2 and 3, were evaluated in non-small cell lung cancer (NSCLC) patients enrolled in NCIC Clinical Trials Group BR.24 comparing chemotherapy with or without cediranib.
Materials and methods: Biomarker levels were assessed by ELISA in serum from 149/296 enrolled patients at baseline and 146/149 patients after one treatment cycle. Experimental cut-offs for baseline measures determined using a graphic method were: VEGF-A: < or >= 1 ng/ml, SDF-1 alpha: <= or > 3.5 ng/ml, sVEGFR2: < or >= 11 ng/ml and sVEGFR3: < or >35.5 ng/ml. Changes in markers from baseline to on-treatment were predefined as increased >10%, stable within 10% or decreased >10%. Cox regression models were used to correlate biomarkers with patient characteristics and outcomes including progression-free survival (PFS) and overall survival (OS).
Results: No baseline biomarker was prognostic for OS, however, high baseline 5VEGFR2 was prognostic for better PFS (p = 0.0008) in the chemotherapy alone arm. Low baseline 5VEGFR2 or 5VEGFR3 were predictive of PFS benefit from cediranib (interaction p = 0.06 and p = 0.05, respectively). While on treatment, VEGFA increases were associated with better PFS (p = 0.02) and OS (p = 0.01) for cediranib treated patients. Decreases in 5VEGFR2 (p = 0.01) or 5VEGFR3 (p = 0.02) were also predictive of better OS in cediranib treated patients.
Conclusions: Low baseline 5VEGFR2 and 5VEGFR3 were predictive for PFS benefit from cediranib, whereas increases in VEGF-A and decreases in sVEGFR2 or 5VEGFR3 levels from baseline to on-treatment were predictive of an OS benefit from cediranib in chemotherapy treated NSCLC patients. Validation of these results is warranted.

• 出版日期2015-11