First-Line Dabrafenib plus Trametinib Has Activity in BRAF^V600E NSCLC

BRAF^V600E mutations drive tumor progression in a subset of patients with non–small cell lung cancer (NSCLC), and effective targeted therapies are needed to achieve better outcomes in these patients. Combined inhibition of BRAF (with dabrafenib) and MEK (with trametinib) achieved responses in a study of patients with previously treated BRAF^V600E-mutant metastatic NSCLC. Based on these findings, Planchard and colleagues evaluated the safety and activity of dabrafenib plus trametinib in an open-label phase II trial of 36 patients with previously untreated BRAF^V600E-mutant metastatic NSCLC. The primary endpoint was overall response, and secondary endpoints included duration of response, progression free-survival, overall survival, and safety assessment. Responses were observed in 23 of 36 patients (64%), including 2 complete responses (6%) and 21 partial responses (58%). Additionally, 4 patients (11%) experienced stable disease. The median duration of response was 15.2 months, the median progression-free survival was 14.6 months, and the median overall survival was 24.6 months. Dabrafenib plus trametinib had a manageable safety profile, and adverse events were consistent with those previously reported. Overall, 69% of patients experienced grade 3–4 adverse events, most commonly pyrexia (11%), alanine aminotransferase increase (11%), hypertension (11%), and vomiting (8%). Taken together, these findings indicate that treatment with dabrafenib plus trametinib achieves antitumor activity and has a manageable safety profile in patients with previously untreated BRAF^V600E-mutant metastatic NSCLC, supporting further investigation of this combination as a first-line therapy in patients with BRAF^V600E-mutant tumors.

Planchard D, Smit EF, Broen HJ, Mazieres J, Besse B, Helland Å, et al. Dabrafenib plus trametinib in patients with previously untreated BRAF^V600E-mutant metastatic non-small-cell lung cancer: an open-label, phase 2 trial. Lancet Oncol 2017 Sep 11 [Epub ahead of print].

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