A New Treatment Receives FDA Approval for BRAF Mutation-Positive Stage 4 Lung Cancer

For BRAF V600E mutation-positive stage 4 - metastatic non-small cell lung cancer, FDA approved the combination of dabrafenib and trametinib (trade names Tafinlar and Mekinist).

Cancer is a group of diseases triggered by genetic changes at cellular level. There are as many main cancer types as organs, and each organ cancer has numerous subtypes. Previously distinguished only by microscopic appearance, subtypes are now identified by cancer cells’ genetic features (certain specific DNA mutations) being sought and detected. In other words, oncology is becoming much more precise. Treatments targeting these cancer-driving DNA mutations are called targeted drugs . The approval granted on 22 June 2017 by FDA represents, for precision medicine , an important development.

For the first time, the United States Food and Drug Administration - FDA approved a drug for BRAF V600E mutation-positive lung cancer.

What Is a BRAF Mutation? How Do Drugs Targeting This Genetic Change Work?

BRAF is a human gene coding for the B-Raf protein, involved in intracellular growth signaling (see figure). In 2002, defective B-Raf proteins resulting from BRAF mutations were first identified in certain human cancers. Vemurafenib and dabrafenib, targeting BRAF mutations in aggressive skin cancer melanoma, had previously received FDA approval. Later studies identified BRAF mutations at certain frequencies in colorectal, thyroid and non-small cell lung cancers too.

The Study Leading to FDA Approval of Dabrafenib and Trametinib for Lung Cancer

This international, multicenter, single-arm study enrolled BRAF V600E mutation-positive patients: 93 with non-small cell lung cancer. They received oral dabrafenib (2 times daily, 150 mg) and trametinib (1 time daily, 2 mg). Of them, 36 had received no systemic treatment for metastatic lung cancer, while 57 had received at least one line of platinum-based chemotherapy. Another 78 had previously used BRAF-targeting dabrafenib alone.

Among patients previously receiving platinum-based chemotherapy, response was %63 and median response duration 12.6 months. In previously untreated patients, response was %61; median response duration was not reached because most responses continued. In those previously receiving dabrafenib alone, response was %27 and median duration 9.9 months.

The most common adverse effects (>%20) were fever, fatigue, nausea-vomiting, diarrhea, dry skin, decreased appetite, edema, rash, bleeding, cough and breathing difficulty-dyspnea.

For non-small cell lung cancer treatment with these drugs, molecular pathology testing of lung tumor biopsy tissue must first demonstrate BRAF V600E mutation positivity. Following FDA approval, we will learn more about their lung cancer use and share developments if they receive approval in our country.