The FDA also approved a diagnostic, the Oncomine Dx Target Test, a next-generation sequencing test to detect gene mutations or alterations, including BRAF, from a single tissue specimen, the FDA reported in a statement.
The approvals are based on overall response rate (ORR) for the combination in a phase II, nonrandomized, noncomparative, open-label trial of patients with locally confirmed BRAF V600E mutation-positive metastatic NSCLC. The ORR for the combination treatment was 61% (95% confidence interval, 44%-77%) among 36 patients who had received no prior systemic therapy for metastatic NSCLC, and 63% (95% CI, 49%-76%) among 57 patients who had received at least one platinum-based chemotherapy regimen with demonstrated disease progression before enrollment. Those 93 patients were all treated with the combination of dabrafenib (150 mg orally twice daily) and trametinib (2 mg orally once daily).
The ORR was 27% (95% CI, 18%-38%) among a third cohort of 78 patients with previously treated BRAF V600E mutation-positive NSCLC who received single-agent dabrafenib.
The most common adverse reactions were similar to those reported in prior approvals for patients with melanoma, including pyrexia, fatigue, nausea, vomiting, diarrhea, dry skin, decreased appetite, edema, rash, chills, hemorrhage, cough, and dyspnea. The most common grade 3-4 adverse reactions were pyrexia, fatigue, dyspnea, vomiting, rash, hemorrhage, and diarrhea. The most common grade 3-4 laboratory abnormalities were hyponatremia, lymphopenia, anemia, hyperglycemia, neutropenia, leukopenia, hypophosphatemia, and increased alanine aminotransferase. Dabrafenib and trametinib were discontinued for adverse reactions in 18% and 19% of patients, respectively, the FDA said.
Novartis is marketing Dabrafenib as Tafinlar and trametinib as Mekinist.
The recommended doses are dabrafenib 150 mg orally twice daily, approximately 12 hours apart, with trametinib 2 mg orally once daily, following confirmation of BRAF V600E mutation in a tumor specimen by an FDA-approved test.