Chicago, IL—In an interim analysis of a single-arm phase 2 study, the BRAF kinase inhibitor dabrafenib (Tafinlar), which was recently approved for the treatment of melanoma, has demonstrated very good efficacy in the treatment of stage IV non–small-cell lung cancer (NSCLC) with the BRAF V600E mutation in patients whose disease progressed after chemotherapy, reported David Planchard, MD, PhD, of the Department of Medical Oncology, Institut Gustave-Roussy, Villejuif Cedex, France, at ASCO 2013.
The safety profile of dabrafenib was consistent with previous studies of this medication in patients with melanoma, said Dr Planchard.
BRAF mutations are found in <2% of patients with NSCLC, and V600E accounts for approximately 50% of these mutations.
The phase 2 study continues to recruit patients with stage IV NSCLC with the BRAF V600E mutation who have undergone ≥1 unsuccessful chemotherapy treatments. The study consists of 2 stages: if the first 20 patients (stage 1) have measurable progress with the use of dabrafenib, then study investigators add 20 more patients (stage 2). If results are encouraging, 20 patients with stage IV NSCLC who had not previously received treatment would become part of an expansion group.
Patients in the trial were administered 150 mg of dabrafenib twice daily until disease progression. The primary end point was overall response rate (ORR). The results were presented for 25 patients, including 20 patients who were evaluable for efficacy. The ORR, which was defined as complete and partial responses plus stable disease, was 60%. A partial response rate was detected in 40% of the patients, and disease stability was realized in 20% of the patients. The disease advanced in 30% of patients.
At the most recent data analysis, 48% of patients were still taking dabrafenib and 52% had discontinued treatment. A durable partial response was reported in 2 patients who have been taking dabrafenib for more than 1 year.
Overall, 24 (96%) patients had an adverse event (AE); 11 (44%) had grade 3 AEs. Most (92%) AEs were related to study treatment; 2 AEs were related to study treatment discontinuation. In addition, AEs in 5 (20%) patients led to dose reduction, and 10 (40%) patients had AEs that resulted in dose interruption.
The most common AEs were fatigue (40%), reduced appetite (32%), rash (24%), nausea (24%), dry skin (20%), and diarrhea (20%). A total of 10 (40%) patients had serious AEs. Of those, 2 patients had squamous-cell carcinoma.
To date, the trial only included a white patient population, Dr Planchard noted. New participants will include an Asian population to help analyze dabrafenib treatment across different races. As the trial goes forward, it will enroll first-line patients as well, he said. The durability of responses still needs to be determined, and the data on progression-free survival are immature.
The results of the study demonstrate that BRAF V600E is “an actionable target beyond melanoma,” said Pasi A. Jänne, MD, PhD, Director, Lowe Center for Thoracic Oncology, Dana-Farber Cancer Institute, Boston, MA, who was not involved in the study.