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Prospective correlative assessment of biomarkers in E4599 randomized phase II/III trial of carboplatin and paclitaxel ± bevacizumab in advanced non-small cell lung cancer (NSCLC)

, : Prospective correlative assessment of biomarkers in E4599 randomized phase II/III trial of carboplatin and paclitaxel ± bevacizumab in advanced non-small cell lung cancer (NSCLC). Journal of Clinical Oncology 24(18_suppl): 7027-7027

NlmCategory="UNASSIGNED">7027 Background: E4599 was a phase II/III trial, in which 878 patients with advanced NSCLC were randomized to carboplatin + paclitaxel (PC arm) or PC + bevacizumab (PCB arm). Survival and progression free survival (PFS) were superior on the PCB arm (Sandler, ASCO 2005). The rationale for markers used in this correlative study were based on elevated vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and soluble intercellular adhesion molecule-1 (ICAM) in NSCLC and changes in response to endothelial apoptosis. Prospective laboratory correlates included measurements of pretreatment plasma VEGF as well as pretreatment and week 7, bFGF, ICAM, and E-Selectin. 166 patients had pre- and 112 had post-treatment measurements. Measurements were made by ELISA. Low and high levels were defined as ≤ or > than the median. There were significant associations between E-Selectin and ICAM (p = .003) and between bFGF and VEGF (p = .01). E-Selectin (p = .01) and bFGF (p = .004) showed significant decreases from baseline at week 7 in both arms (Wilcoxon signed-rank tests). Only baseline ICAM showed a significant association with response. Patients with low baseline ICAM in both arms had a higher response rate of 29% vs 13% in high ICAM group (p=0.03, Fisher's exact test). Patients with low baseline ICAM levels had a significantly better overall survival (p=0.00005) compared to patients with high ICAM levels as well as a better 1-year survival (65% vs 25%). No other factor predicted survival. Tests for treatment by factor interactions, which test whether the effect of treatment (the addition or not of bevacizumab) is different within the low and high levels were significant only for baseline ICAM where treatment interaction is significant for PFS (p=.04). This suggests a benefit from bevacizumab (53% reduction in the PFS hazard rate) in the group with low baseline ICAM levels vs no benefit from bevacizumab for patients with high levels. Baseline ICAM levels are strongly prognostic for survival and response to chemo. This exploratory correlative study suggests that improvements in PFS from the addition of bevacizumab occur mainly in patients with low baseline ICAM levels. [Table: see text].


PMID: 27953211

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