On 6/22/17, the US Food and Drug Administration (FDA) granted full approvals to two targeted therapies to be used in combination for patients with metastaticnon-small cell lung cancer (NSCLC) with BRAF V600E mutation as detected by an FDA-approved test. The two newly-approved targeted therapies, Tafinlar (dabrafenib) and Mekinist (trametinib), are both from Novartis Pharmaceuticals. These are the first FDA approvals specifically for the treatment of patients with BRAF V600E-positive metastatic NSCLC. The FDA also approved a new test, Oncomine Dx Target Test, from ThermoFisher Scientific, that can detect gene mutations (including BRAF, ROS1, and EGFR) with a single tissue simple.1
“The approval of Tafinlar + Mekinist makes BRAF V600E the fourth actionable genomic biomarker in metastatic NSCLC – along with EGFR, ALK and ROS-1… This is an important milestone for the lung cancer community as we are continuing to better understand the genomic drivers of cancer and develop effective treatments targeted for these biomarkers,” said Bruce Johnson, MD, Professor of Medicine, Chief Clinical Research Officer, Dana-Farber Cancer Institute and Harvard Medical School at Dana-Farber Cancer Institute.2
Clinical Trial Results
The approvals of Tafinlar and Mekinist, which are currently approved for advanced melanoma, were based on Study BRF113928. This study was a non-randomized, non-comparative, open label trial for patients with metastatic NSCLC and confirmed BRAF V600E mutation. Among patients who had not previously received treatment, the combination treatment resulted in an overall response rate (ORR), or the proportion of patients with reduced tumor size, of 61%. Among those patients having received lung cancer treatment prior to the study, the combination therapy resulted in a 63% ORR. Patients who received the combination of Tafinlar and Mekinist had a better response rate than those who only received Tafinlar (ORR=27%).3
All cells have coded instructions in their genes. When changes occur to the genes, the cells change their normal behavior and can become cancer cells. Each cancer is unique and has different genetic changes. As cancers grow, additional genetic changes can occur. Scientists have found that there are certain changes, or mutations, that commonly occur in many types of cancers, including lung cancer. These mutations are often a target for potential treatments to stop the cancer. In NSCLC, researchers have identified several genetic mutations that are known to play an important role in the development and progression of the lung cancer.4,5 Mutations on the BRAF gene have been found in 1-4% of all NSCLC and most often occurs in adenocarcinomas.6
FDA Approves Targeted Drug Combo for Lung Cancer. Medscape. Available at: http://www.medscape.com/viewarticle/882058
Novartis combination targeted therapy Tafinlar® + Mekinist® receives FDA approval for BRAF V600E mutant metastatic non-small cell lung cancer (NSCLC). Novartis Media Release. Available at: https://www.novartis.com/news/media-releases/novartis-combination-targeted-therapy-tafinlarr-mekinistr-receives-fda-approval
FDA grants regular approval to dabrafenib and trametinib combination for metastatic NSCLC with BRAF V600E mutation. US Food and& Drug Administration. Approved Drugs News Release. Available at: https://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm564331.htm?
National Cancer Institute. Accessed online on 8/1/16 at http://www.cancer.gov/
NCCN Guidelines for Patients. Non-Small Cell Lung Cancer. Version 1.2015. Accessed April 11, 2016 at http://www.nccn.org/patients/guidelines/nscl/index.html.
My Cancer Genome. Accessed online on 8/11/16 at https://www.mycancergenome.org/.