Dabrafenib and Trametinib Gets Accelerated Approval by FDA for NSCLC treatment

June 2017

The Food and Drug Administration (FDA) granted accelerated approval to the dabrafenib and trametinib (Tafinlar and Mekinist, Novartis Pharmaceuticals, Inc) administered in combination to patients with metastatic Non-Small Cell Lung Cancer (NSCLC) whose tumors are found to harbor the BRAF mutation V600E as detected by an FDA-approved genetic alteration test. The FDA also approved the Oncomine Diagnostic Target Test (Thermo Fisher Scientific), a DNA sequencing test used to identify genetic mutations for lung cancer in a single test from a lung biopsy sample.  The test detects gene mutations in BRAF, ROS1 and EGFR genes from single tumor samples.  This test can therefore be used to identify patients with BRAF V600E mutations in their tumor, making them eligible for treatment with the combination of dabrafenib and trametinib drugs.  The approval of this drug combination and the test to identify the relevant tumor mutation was approved based on a study, NCT01336634, an international, multicenter clinical trial in patients with confirmed BRAF V600E mutation-positive metastatic NSCLC.  In the group of patients previously treated with other therapies, the overall response rate (ORR) for the drug combination was 63%, with an average duration of response of 12.6 months.  In the group of patients who had not been previously treated, the ORR for the combination treatment was 61%; However the median duration of response for this group could not be estimated during the time period of the study.  However, 59% of patients who had positive responses to the drug combination had response durations greater than 6 months.  In 2015, the FDA had previously granted Breakthrough Designation for the combination of dabrafenib and trametinib for the treatment of patients with advanced and metastatic BRAF V600E mutations in their NSCLC tumors who had received at least one prior line of platinum therapy.  Prior to that, Orphan Drug Designation was granted by the FDA in 2014 for the use of dabrafenib as a single agent for the treatment of NSCLC patients whose tumors contained a BRAF mutation, and subsequently in 2015 for combined treatment with trametinib.