Dr Cappuzzo has received payment
for consultancy or advisory roles from Roche. Dr Brugger has received honoraria and payment for consultancy or advisory roles from Roche. Dr Middel has received other remunerations from F. Hoffmann-La Roche Ltd. Dr Frosch has declared no conflicts of interest. This trial was designed, funded by and monitored by F. Hoffmann-La Roche Ltd. Data were collected, analyzed and interpreted by F. Hoffmann-La Roche, with input from the authors and investigators. The initial draft Dabrafenib clinical trial of the manuscript was reviewed and commented on by all authors, and by employees of F. Hoffmann-La Roche. The corresponding author had full access to the study data and took full responsibility for the final decision to submit the paper. Support for third-party writing assistance from Gardiner-Caldwell Communications for this manuscript was provided by F. Hoffmann-La Roche Ltd. “
cancer is the leading cause of cancer-related death worldwide , with recent statistics projecting 226,160 new cases in the US alone in 2012 . Current therapeutic options for first-line non-small cell lung cancer (NSCLC) treatment are based on platinum doublet chemotherapy, which provide overall survival (OS) of ∼8 months . Advances in treatments include personalized NSCLC therapies that focus on molecular targets to improve outcomes and reduce cumulative toxicities seen with chemotherapies. For patients with epidermal growth factor (EGFR) mutations, EGFR tyrosine-kinase
inhibitors (TKIs) are recommended as first-line therapy, for those with non-squamous disease without these driver mutations, agents Protease Inhibitor Library such as pemetrexed and bevacizumab are available . Bevacizumab is a recombinant humanized monoclonal antibody against vascular endothelial growth factor (VEGF). VEGF is a key signaling molecule in developmental angiogenesis, promoting survival of endothelial cells and new vessel growth . Tumor dependency on VEGF makes VEGF an attractive target for anti-cancer treatments. The addition of bevacizumab to chemotherapy, improved OS with first-line paclitaxel and carboplatin (12.3 months for bevacizumab plus chemotherapy, hazard ratio [HR] 0.79, 95% confidence interval [CI]: 0.67–0.92; p = 0.003) . The first-line AVAiL study showed increased Carbachol progression-free survival (PFS) with the addition of bevacizumab to cisplatin–gemcitabine (HR 0.75, 95% CI: 0.64–0.87; p = 0.0003) . In a phase IV trial bevacizumab-based therapy resulted in median OS of 14.6 months (95% CI 13.8–15.3) . Erlotinib is an EGFR TKI. EGFR is critical in pathways used in cell proliferation and survival and increased expression is often seen in tumor cells . Erlotinib demonstrated a significant OS benefit versus placebo (HR 0.70, 95% CI: 0.58–0.85; p < 0.001) in patients with advanced NSCLC who had failed prior chemotherapy in a randomized, double-blind trial (BR.21)  and .