FDA Approves First Treatment for Specific Genetic Mutation of NSCLC

The US Food and Drug Administration recently granted regular approval to the combination of dabrafenib and trametinib for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) with BRAF V600E mutation, which is the first approval for the treatment of this specific mutation of NSCLC.

Dabrafenib is recommended to be administered twice a day, approximately 12 hours apart, orally at a dose of 150 mg, and trametinib is recommended to be administered once a day, orally, at a dose of 2 mg.
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In addition, the FDA approved the Oncomine™ Dx Target Test for the detection of multiple gene mutations for lung cancer in a single test from a single tissue, including BRAF mutations. This is the first oncology panel test approved for multiple companion diagnostic indications, and can be used to select patients with NSCLC with the BRAF V600E mutation for treatment with the combination of dabrafenib and trametinib.

The efficacy of combined dabrafenib and trametinib was determined in a multicentered, 3-cohort, non-randomized, non-comparative, open label trial. The trial included 93 patients with BRAF V600E mutation-positive metastatic NSCLC who were treated with 150 mg orally administered dabrafenib and 2 mg orally administered trametinib. The overall response rate (ORR) of the 57 patients who received prior treatment with at least one platinum-based chemotherapy regimen was 63%, and the median duration of response (DoR) was 12.6 months. Among the 36 patients who had not received prior systemic treatment, the ORR was 61% and the median DoR was not estimable, but 59% of those who responded had a response duration greater than 6 months.

Additionally, 78 patients who had previously treated BRAF V600E mutation-positive NSCLC received single-agent dabrafenib and had an ORR of 27% and median DoR of 9.9 months.

The most common adverse reactions that occurred in 20% or more of patients included pyrexia, fatigue, nausea, vomiting, diarrhea, dry skin, decreased appetite, edma, rash, chills, hemorrhage, cough, and dyspnea. Common Grade 3 or 4 laboratory abnormalities that occurred in 5% or more of patients included hyponatremia, lymphopenia, anemia, hyperglycemia, neutropenia, leukopenia, hypophosphatemia, and increased alanine aminotransferase. Dabrafenib was discontinued in 18% of patients and trametinib was discontinued in 19% of patients due to adverse reactions.

—Melissa Weiss

Reference:

FDA grants regular approval to dabrafenib and trametinib combination for metastatic NSCLC with BRAF V600E mutation [press release]. FDA. June 22, 2017. https://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm564331.htm?source=govdelivery&utm_medium=email&utm_source=govdelivery. Accessed June 23, 2017.