Combining Targeted Therapies for Lung Cancer
An FDA-approved precision medicine treatment is for certain patients with metastatic lung cancer with a specific BRAF mutation.
The U.S. Food and Drug Administration (FDA) recently approved the molecularly targeted therapeutics dabrafenib (Tafinlar) and trametinib (Mekinist) for use in combination to treat patients with metastatic non-small cell lung cancer (NSCLC) harboring a mutation in the BRAF gene called BRAF V600E.
NSCLC is the most common type of lung cancer diagnosed in the United States. In fact, it is estimated to account for 84 percent of lung cancer cases, which translates into 186,900 new cases expected to be diagnosed in 2017.
This approval of a precision medicine for NSCLC was built upon prior research on melanoma. It was the discovery that 50 percent of melanomas are fueled by the abnormal BRAF V600E protein generated as a result of the BRAF V600E mutation that led to the development of several BRAF V600E-targeted therapeutics, including dabrafenib. It also led to the development of several therapeutics, including trametinib, that block the activity of two other proteins, MEK1 and MEK2, that function in the same signaling network as BRAF V600E. The combination of dabrafenib and trametinib was approved by the FDA for treating melanoma with BRAF mutations, including BRAF V600E mutations, in January 2014.
After learning that the BRAF V600E protein also fuels the growth of NSCLC in 1 to 2 percent of patients with this disease, researchers sought to test whether the dabrafenib and trametinib combination might be an effective treatment in this setting.
According to the FDA, results from the BRF113928 phase II clinical trial, which led to the approval, showed that treatment with the combination of dabrafenib and trametinib led to complete or partial tumor shrinkage in about 60 percent of patients.
Alongside the approval of dabrafenib and trametinib, the FDA also approved a companion diagnostic to identify patients eligible for the new combination treatment, those who have NSCLC with a BRAF V600E mutation.
This is not the first example of a precision medicine for treating lung cancer. In fact, NSCLC is one of the types of cancer that has been at the forefront of the implementation of precision medicine in oncology because research provided extensive insight into the genetic mutations that fuel NSCLC growth in certain subgroups of patients and led to the development of therapeutics that target the effects of these mutations. It is, however, the first precision medicine approved for patients with BRAF V600E-positive NSCLC.
The FDA approval was rendered on June 22, 2017.