A next generation sequencing test to detect lung cancer mutation was also approved.
The FDA granted approval to combination treatment dabrafenib and trametinib (Tafinlar and Mekinist) for patients with metastatic non-small cell lung cancer (NSCLC) with BRAF V600E mutation.
These are the first specific approvals granted for the treatment of patients with BRAF V600E mutation-positive metastatic NSCLC, according to a press release.
Additionally, the FDA also approved a next-generation sequencing test (NGS), called the Oncomine Dx Target Test, to detect multiple gene mutations for lung cancer using a single test from a single tissue specimen.
NGS is approved to detect the presence of BRAF, ROS1, and EGFR mutations or alterations in the tumor tissue of patients with NSCLC, according to a release. It can be used to identify the BRAF V600E mutation in patients with NSCLC to place on the combination treatment.
The approvals are based on the international, multicenter, 3-cohort, non-randomized, non-comparative, open-label BRF113928 trial of patients with locally confirmed BRAF V600E mutation-positive metastatic NSCLC.
For the study, 93 patients were treated with the combination oral treatment of 150 mg of dabrafenib twice-daily plus 2 mg of trametinib once-daily. Of the 93 patients, 36 had not received prior systemic therapy for their cancer and 57 received at least 1 platinum-based chemotherapy regimen resulting in disease progression. Seventy-eight patients with previously untreated BRAF V600E mutation-positive NSCLC received dabrafenib monotherapy.
The results of the study showed that the overall response rate (ORR) for patients who received the combination treatment was 63%, with a median duration of response (DoR) of 12.6 months. Patients in the treatment-naïve arm who received the combination achieved an ORR of 61%. Although the median DoR was not estimable, 59% of responders had a response that lasted longer than 6 months, according to the release.
For patients administered the single-agent dabrafenib, the ORR was 27% and the median DoR was 9.9 months.
The most common adverse events (AEs) were pyrexia, fatigue, nausea, vomiting, diarrhea, dry skin, decreased appetite, edema, rash, chills, hemorrhage, cough, and dyspnea. The most common grade 3 and 4 AEs were pyrexia, fatigue, dyspnea, vomiting, rash, hemorrhage, and diarrhea.
Most of the laboratory abnormalities were grade 1 and 2, according to the release. The most common grade 3 and 4 laboratory abnormalities were hyponatremia, lymphopenia, anemia, hyperglycemia, neutropenia, leukopenia, hypophosphatemia, and increased alanine aminotransferase.
The approved recommended doses are 150 mg of dabrafenib twice-daily, approximately 12 hours apart, plus 2 mg of trametinib orally once-daily.
“The presence of BRAF V600E mutation in tumor specimen should be confirmed by an FDA-approved test prior to initiation of therapy,” the release stated.