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Clin Cancer Res. 2013 Dec 15;19(24):6967-75. doi: 10.1158/1078-0432.CCR-12-1818. Epub 2013 Oct 28.

Comprehensive biomarker analysis and final efficacy results of sorafenib in the BATTLE trial.

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Authors' Affiliations: Departments of Thoracic/Head and Neck Medical Oncology, Biostatistics and Applied Mathematics, Translational Molecular Pathology, Diagnostic Imaging, Diagnostic Radiology, and Bioinformatics and Computational Biology; Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston; The Hamon Center for Therapeutic Oncology Research and Departments of Internal Medicine and Pharmacology, The University of Texas Southwestern Medical Center, Dallas, Texas; Solid Tumor Oncology and Investigational Therapeutics, Levine Cancer Institute, Charlotte, North Carolina; Medical Oncology, Yale Cancer Center, New Haven, Connecticut; Division of Medical Oncology, University of Ottawa, Ottawa, Ontario; Department of Oncology and Diagnostic Sciences, University of Maryland Dental School, Baltimore, Maryland; UC San Diego Moores Cancer Center, La Jolla, California; and Centre de Recherche en Cancérologie de Lyon, UMR INSERM 1052-CNRS 5286, Centre Léon Bérard, Lyon, France.



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.


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 K-RAS, EGFR, and B-RAF mutations, and EGFR gene copy number. Gene expression profiles from NSCLC cell lines and patient tumor biopsies with wild-type EGFR were used to develop a sorafenib sensitivity signature (SSS).


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 EGFR than patients with EGFR mutation (P = 0.012), and in patients with EGFR gene copy number gain (FISH-positive) versus patients FISH-negative (P = 0.048). In wild-type EGFR tumors, the SSS was associated with improved PFS (median PFS 3.61 months in high SSS vs. 1.84 months in low SSS; P = 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.


Sorafenib demonstrates clinical activity in NSCLC, especially with wild-type EGFR. SSS was associated with improved PFS. These data identify subgroups that may derive clinical benefit from sorafenib and merit investigation in future trials.

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