Gefitinib failed to demonstrate superior OS compared with GP as first-line therapy for NSLAs.

Purpose: To evaluate the efficacy and safety of gefitinib plus simvastatin (GS) versus gefitinib alone (G) in previously treated patients with advanced non-small cell lung cancer (NSCLC).Experimental Design: Between May 2006 and September 2008, 106 patients (51% men, 75% adenocarcinoma, 50% never smoker) were randomly assigned to G alone (250 mg/d, n ¼ 54) or GS (250 and 40 mg/d, respectively, n ¼ 52). One cycle was 4 weeks of treatment. Therapy was continued until disease progression or intolerable toxicity was observed. The primary endpoint was response rate (RR). Secondary endpoints included toxicity, progression-free survival (PFS), and overall survival (OS).Results: The RR was 38.5% (95% CI, 25.3-51.7) for GS and 31.5% (95% CI, 19.1-43.9) for G. The median PFS was 3.3 months [M] (95% CI, 1.4-5.2M) for GS and 1.9M (95% CI, 1.0-2.8M) for G. The median OS was 13.6M (95% CI, 7.1-20.1M) for GS and 12.0M (95% CI, 7.8-16.2M) for G. In exploratory subgroup analysis, GS showed higher RR (40% vs. 0%, P ¼ 0.043) and longer PFS (3.6M vs.

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Purpose: Circulating cell-free DNA (CFDNA) was investigated as potential screening or prognostic markers in a variety of cancers. This study investigated its clinical significance in a homogeneous group of lung cancer patients.Experimental Design: We analyzed the blood samples of 134 never smokers with advanced lung adenocarcinoma, who were enrolled in a prospective randomized phase III study (First-SIGNAL) comparing gefitinib with gemcitabine plus cisplatin (GP) as first-line therapy. The amount of plasma CFDNA was measured by real-time quantitative PCR targeting the human ACTB genomic sequence. The patients were divided into three groups according to the tertiles of baseline plasma CFDNA.Results: Baseline plasma CFDNA did not correlate with primary tumor size (P ¼ 0.961), whereas the number of metastatic sites correlated significantly with baseline plasma CFDNA (P ¼ 0.015). In the GP arm, the low-CFDNA group showed a lower response rate than the middle-or high-CFDNA group (26.1%, 57.9%, and 60.9%, respectively; P ¼ 0.035). However, in the gefitinib arm, there was no difference in response rate between the three CFDNA groups (57.1%, 47.4%, and 51.9%; respectively; P ¼ 0.825). The high tertile CFDNA group showed a significantly shorter survival than the low tertile CFDNA group (median overall survival, 16.0 vs. 28.6 months, respectively; P ¼ 0.030). The risk of death increased with increased baseline plasma CFDNA (HR ¼ 1.23, 95% CI, 1.01-1.50; P ¼ 0.045).Conclusion: High plasma CFDNA is associated with aggressive tumor behavior and poor survival outcomes in these patients. Clin Cancer Res; 17(15); 5179-87. Ó2011 AACR.