In a phase II trial, the combination of dabrafenib (Tafinlar) plus trametinib (Mekinist) produced durable responses in a cohort of patients with previously untreated BRAF V600E–mutant metastatic non–small cell lung cancer (NSCLC). The findings were reported in The Lancet Oncology by Planchard et al.
In the multicohort, multicenter trial, 36 patients were enrolled between April 2014 and December 2015 and treated with first-line oral dabrafenib at 150 mg twice daily plus oral trametinib at 2 mg once daily until disease progression or unacceptable toxicity. The primary endpoint was investigator-assessed overall response.
Median follow-up was 15.9 months at the data cutoff in April 2017. Confirmed objective response was observed in 23 patients (64%), including a complete response in 2 (6%). Stable disease was observed in an additional four patients (11%). Median duration of response was 10.4 months. Median progression-free survival was 10.9 months. Median overall survival was 24.6 months.
Grade 3 or 4 adverse events occurred in 69% of patients, with the most common being pyrexia (11%), alanine transaminase (ALT) increase (11%), hypertension (11%), and vomiting (8%). The most common serious adverse events were ALT increase (14%), pyrexia (11%), aspartate transaminase increase (8%), and ejection fraction decrease (8%). Adverse events led to treatment discontinuation in 22% of patients.
The investigators concluded: “Dabrafenib plus trametinib represents a new therapy with clinically meaningful antitumour activity and a manageable safety profile in patients with previously untreated BRAF V600E-mutant NSCLC.”
The study was funded by Novartis.
Bruce E. Johnson, MD, of Dana-Farber Cancer Institute, is the corresponding author of The Lancet Oncology article.
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