Abstract
8018 Background: This multicentre, phase II study evaluates efficacy and safety of erlotinib, an EGFR inhibitor, and sorafenib, a multi-kinase inhibitor, in advanced NSCLC. In addition circulating endothelial cell (CEC) numbers, plasma VEGF, tumor metabolic activity (18FDG-PET), and tumor blood flow (H215O-PET) were measured. Methods: Chemotherapy-naive patients (≥ 18 years; performance status 0–1) with pathologically proven irresectable stage IIIB or IV NSCLC were eligible. Pts received erlotinib (150 mg/od) and sorafenib (400 mg/bd) until disease progression or unacceptable toxicity. The planned sample size was 48. The primary endpoint was the rate of non-progression (NPR) at 6 weeks. Secondary endpoints: objective response rate (RECIST), time to progression (TTP), overall survival (OS) and adverse events (AEs). CECs, characterized by CD45neg/CD34bright, and plasma VEGF were measured in blood samples on days (D)0, 7, 21. 18FDG-PET and H215O-PET were performed on D0, 21. Results: 50 pts were enrolled: 22 females; median age 60 yrs (range 41–78); 30 PS 0; 37 stage IV; 34 adenocarcinoma; 11 never smokers; 10/33 EGFR mutations (exons 19 (n=5), 20 (n=1), 21 (n=4)); 3/33 K-Ras mutations. Median FU is 3.3 mo (range 0.2–10.8) with 20 pts on therapy. The NPR at 6 weeks was 76%: 13 PR, 25 SD, 8 PD, 4 NE. Median TTP is 4.6 mo (95% CI 2.6–6.6). Median OS has not been reached. Grade ≥ 3 AE: anorexia (n=1), acneiform rash (n=5), diarrhoea (n=6), fatigue (n=4), hand-foot skin reaction (n=6), nausea (n=2), oral mucositis (n=2), rash (n=5), vomiting (n=1) and fatal hemoptysis (n=1). Median CECs (n=24) and plasma VEGF (n=25) increased from 41cells/ml D0 to 124 D7 (p=0.001) to 148 D21 (p=0.000) and 44pg/ml D0 to 60 D7 (p= 0.024), respectively. 18FDG SUV (n=28) decreased by median 35% (p=0,000). 18FDG SUV decreased more in clinical (RECIST) responders than non-responders (-51% vs -18.5%, p=0.031). Tumor blood flow (n=14) decreased by median 11% (n.s). Relations of these biomarkers with TTP and survival will be provided. Conclusions: The combination of sorafenib and erlotinib is safe and has clinically significant anti-tumor activity in chemotherapy-naive patients with stage IIIB/IV NSCLC, with significant changes in CECs, VEGF, and metabolic tumor activity. No significant financial relationships to disclose.
Published Version
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