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

George R. Blumenschein, Pierre Saintigny, Suyu Liu, Edward S. Kim, Anne S. Tsao, Roy S. Herbst, Christine Alden, J. Jack Lee, Ximing Tang, David J. Stewart, Merrill S. Kies, Frank V. Fossella, Hai T. Tran, L. Mao, Marshall E. Hicks, Jeremy Erasmus, Sanjay Gupta, Luc Girard, Michael Peyton, Lixia DiaoJing Wang, Suzanne E. Davis, John D. Minna, Ignacio Wistuba, Waun K. Hong, John V. Heymach, Scott M. Lippman

Research output: Contribution to journalArticlepeer-review

53 Scopus citations


Purpose: 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 and Methods: Patients with previously treated non-small cell lung cancer (NSCLC) received sorafenib until progression or unacceptable toxicity. Eight-week disease control rate (DCR), progressionfree 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). Results: 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-kB, and hypoxia pathways were identified potential drivers of sorafenib resistance. Conclusion: 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.

Original languageEnglish (US)
Pages (from-to)6967-6975
Number of pages9
JournalClinical Cancer Research
Issue number24
StatePublished - Dec 15 2013

ASJC Scopus subject areas

  • Medicine(all)


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