Dabrafenib and Trametinib in BRAF V600E–Mutant Metastatic NSCLC
Treatment-naive patients with BRAF V600E–mutant non–small cell lung cancer (NSCLC) have experienced “clinically meaningful” antitumor activity and a “manageable” safety profile when treated with dabrafenib plus trametinib, according to a recent phase II clinical trial. David Planchard, MD, of Gustave Roussy in Villejuif, France, and colleagues reported the findings from an ongoing study in The Lancet Oncology. BRAF V600E is an oncogenic driver found in 1% to 2% of lung adenocarcinomas.
In what the investigators are calling the first report of the use of BRAF and MEK inhibitor combination in the first-line setting for NSCLC, the treatment yielded a high proportion of durable responses. In this median follow-up of 10.4 months, 64% of patients had achieved a complete response and 58%, a partial response.
All of the patients had at least one adverse event, and 69% had at least one grade 3 or 4 event. Pyrexia, alanine aminotransferase level increase, hypertension, and vomiting were the most common grade 3 or 4 adverse events reported.
Although targeted, genotype-directed therapies for patients with driver mutations have improved outcomes in some patients, nearly half the patients do not respond to these treatments. “Therefore, an unmet need remains for effective targeted agents in this population,” Dr. Planchard and colleagues noted.