Data from Comprehensive Biomarker Analysis and Final Efficacy Results of Sorafenib in the BATTLE Trial

Abstract

<div>Abstract<p><b>Purpose:</b> To report the clinical efficacy of sorafenib and to evaluate biomarkers associated with sorafenib clinical benefit in the BATTLE (Biomarker-Integrated Approaches of Targeted Therapy for Lung Cancer Elimination) program.</p><p><b>Patients and Methods:</b> Patients with previously treated non–small cell lung cancer (NSCLC) received sorafenib until progression or unacceptable toxicity. Eight-week disease control rate (DCR), progression-free survival (PFS), and overall survival (OS) were assessed. Prespecified biomarkers included <i>K-RAS</i>, <i>EGFR</i>, and <i>B-RAF</i> mutations, and <i>EGFR</i> gene copy number. Gene expression profiles from NSCLC cell lines and patient tumor biopsies with wild-type <i>EGFR</i> were used to develop a sorafenib sensitivity signature (SSS).</p><p><b>Results:</b> A total of 105 patients were eligible and randomized to receive sorafenib. Among 98 patients evaluable for eight-week DCR, the observed DCR was 58.2%. The median PFS and OS were 2.83 [95% confidence interval (CI), 2.04–3.58] and 8.48 months (95% CI, 5.78–10.97), respectively. Eight-week DCR was higher in patients with wild-type <i>EGFR</i> than patients with <i>EGFR</i> mutation (<i>P</i> = 0.012), and in patients with <i>EGFR</i> gene copy number gain (FISH-positive) versus patients FISH-negative (<i>P</i> = 0.048). In wild-type <i>EGFR</i> tumors, the SSS was associated with improved PFS (median PFS 3.61 months in high SSS vs. 1.84 months in low SSS; <i>P</i> = 0.026) but not with eight-week DCR. Increased expression of fibroblast growth factor-1, NF-κB, and hypoxia pathways were identified potential drivers of sorafenib resistance.</p><p><b>Conclusion:</b> Sorafenib demonstrates clinical activity in NSCLC, especially with wild-type <i>EGFR</i>. SSS was associated with improved PFS. These data identify subgroups that may derive clinical benefit from sorafenib and merit investigation in future trials. <i>Clin Cancer Res; 19(24); 6967–75. ©2013 AACR</i>.</p></div>