The US Food and Drug Administration (FDA) approved the combination of dabrafenib and trametinib for metastatic non–small cell lung cancer (NSCLC) with a BRAFV600E mutation. This is the first time the FDA has approved treatments specifically for BRAFV600E-positive metastatic NSCLC.
Also approved was the Oncomine Dx Target Test, a next-generation sequencing (NGS) test to detect the presence of BRAF, ROS1, and EGFR gene mutations, as well as changes in tumor tissue.
The FDA based its approvals on the results from Study BRF113928 (ClinicalTrials.gov Identifier: NCT01336634), an international, multicenter, 3-cohort, non-randomized, non-comparative, open-label trial that enrolled 93 patients with BRAFV600E-positive NSCLC.
Fifty-seven patients were previously treated with a platinum-based chemotherapy regimen and 36 were treatment naïve.
In previously treated patients, the overall response rate (ORR) was 63% (95% CI: 49%-76%) and the median duration of response (DoR) was 12.6 months (95% CI, 5.8-not estimable). The ORR in the treatment naïve group was 61% (95% CI: 44%-77%) and median DoR was not estimable (95% CI, 6.9-NE).
Patients who received single-agent dabrafenib had an ORR of 27% (95% CI: 18%-38%) and median DoR of 9.9 months. The ORR was determined by an independent review committee.
Treatment should be initiated only once the BRAFV600E mutation is confirmed by an FDA-approved test.
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The recommended dosages are trametinib 2 mg once daily and dabrafenib 150 mg every 12 hours.
The most commonly observed adverse reactions (occurring in at least 20% of patients) were nausea, vomiting, diarrhea, decreased appetite, pyrexia, fatigue, edema, chills, cough, dyspnea, dry skin, rash, and hemorrhage.
- FDA grants regular approval to dabrafenib and trametinib combination for metastatic NSCLC with BRAF V600E mutation [news release]. Silver Spring, MD: US Food and Drug Administration; June 22, 2017. https://www.fda.gov/Drugs/InformationOnDrugs/ ApprovedDrugs/ucm564331.htm. Accessed June 22, 2017.