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.

No abstract

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.

A high posttreatment NLR is associated with poor prognosis. An early reduction in the NLR after effective treatment may indicate survival improvement in the patients with poor prognosis.

No abstract

While no significant difference in OS was observed between EGFR exon 19 deletion and L858R mutation, EGFR exon 19 deletion was predictive of longer PFS following EGFR TKI treatment in patients with advanced NSCLC.

BACKGROUND: Epidermal growth factor receptor (EGFR) T790M mutation drives acquired drug resistance to EGFR tyrosine kinase inhibitors (EGFR-TKIs) in patients with EGFR-mutant lung cancer. However, it was reported that this mutation may exist before drug exposure. The objective of the current study was to evaluate whether the clinical outcomes are affected by the percentage of preexisting T790M mutations within a tumor. METHODS: Pretreatment tissues were collected from 124 patients with advanced non-small cell lung cancer with sensitizing EGFR mutations that were detected by direct sequencing. Genotyping for EGFR T790M mutation was further performed using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Patients who were positive for the T790M mutation were divided to 2 subgroups according to T790M mutant signal frequency. RESULTS: The T790M mutation was found in 31 patients (25.0%). The T790M mutation frequency at which the risk of disease progression after therapy with EGFRTKIs begins to increase was estimated to be 3.2%. The patients with T790M-positive tumors had a shorter time to disease progression after treatment with EGFR-TKIs (median, 6.3 months vs 11.5 months; P <.001) and overall survival (median, 16.1 months vs 26.5 months; P 5.065) compared with those with T790M-negative tumors. Among the T790M-positive patients, the patients with high T790M frequency (9 patients) were found to have a shorter time to disease progression (median, 2.4 months vs 6.7 months; P 5.009) and overall survival (median, 9.1 months vs 18.7 months; P 5.018) compared with those with low T790M frequency (22 patients). CONCLUSIONS: A preexisting EGFR T790M mutation was noted in 25% of patients with EGFR-mutant lung cancer. Patients with a high T790M mutation frequency had worse clinical outcomes to EGFR-TKIs than patients with a low T790M mutation frequency.