Using a biomarker-integrated approach to evaluate various therapies in previously treated patients with advanced non-small cell lung cancer (NSCLC), researchers found that MK-2206 plus AZD6244 (selumetinib) improves progression-free survival of patients with a KRAS mutation.1

The Biomarker-Integrated Approaches of Targeted Therapy for Lung Cancer Elimination (BATTLE) trial previously established the use of real-time biopsy, biomarker-based, adaptively randomized studies in NSCLC. Researchers conducted the BATTLE-2 umbrella study to evaluate the effects of targeted therapies, particularly in patients with advanced, KRAS­-mutant disease.

Investigators enrolled 200 patients with advanced NSCLC who did not have sensitizing EGFR mutations or ALK gene fusions. All participants were refractory to at least 2 prior therapies and 27% had KRAS-mutant tumors.

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Patients were randomly assigned to receive erlotinib (arm 1), erlotinib plus the AKT inhibitor MK-2206 (arm 2), MK-2206 plus the MEK inhibitor AZD6244 (arm 3), or sorafenib (arm 4). Tumor gene expression profiling–targeted next-generation sequencing was also used to assess predictive and prognostic biomarkers.

Among the 186 evaluable patients, the 8-week disease control rate was 32% for erlotinib, 50% for erlotinib plus MK-2206, 53% for MK-2206 plus AZD6244, and 46% for sorafenib. The overall disease control rate was 48%.

Among patients with KRAS-mutant tumors, the disease control rate was 20%, 25%, 62%, and 44%, compared with 36%, 57%, 49%, and 47% in patients with KRAS wild-type tumors for arms 1, 2, 3, and 4, respectively.

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Researchers also observed a significant difference in median progression-free survival between arms, with therapies not containing erlotinib resulting in improved progression-free survival in KRAS mutation-positive patients (P = .04).

Despite these findings, the authors note that better biomarker-driven treatment strategies are still needed.                          


  1. Papadimitrakopoulou V, Lee JJ, Wistuba II, et al. The BATTLE-2 study: A biomarker-integrated targeted therapy study in previously treated patients with advanced non–small-cell lung cancer. J Clin Oncol. 2016 Aug 1. doi: 10.1200/JCO.2015.66.0084 [Epub ahead of print]