FDA Approves Combo Tx for Metastatic NSCLC with BRAF V600E Mutation

These are the first agents to receive approval for this specific indication
These are the first agents to receive approval for this specific indication

Novartis announced that the Food and Drug Administration (FDA) has approved Tafinlar (dabrafenib) and Mekinist (trametinib) combination therapy for patients with metastatic non-small cell lung cancer (NSCLC) positive for BRAF V600E mutation as detected by an FDA-approved test. Tafinlar and Mekinist are the first agents to receive approval for this specific indication.

In 2015, dabrafenib and trametinib combination therapy was granted Breakthrough Therapy Designation for the treatment of advanced and metastatic BRAF V600E mutation-positive NSCLC in patients who had received at least one prior line of platinum-containing therapy.

The approval for Tafinlar and Mekinist combination therapy was based on a Phase 2 international, multicenter, 3-cohort, non-randomized, non-comparative, open-label trial (Study BRF113928) in patients with locally confirmed stage IV NSCLC with BRAF V600E mutation. Thirty-six treatment-naïve patients and 57 platinum-based chemotherapy-experienced patients were treated with the fixed combination of dabrafenib 150mg twice daily and trametinib 2mg once daily. Seventy-eight patients previously treated for BRAF V600E mutation-positive NSCLC received single-agent dabrafenib. 

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The three cohorts were assessed for overall response rate (ORR) and median duration of response (DoR), if available. In the treatment-naïve group, the ORR for the combination was 61% (95% CI: 44%, 77%) and median DoR was not estimable (NE). The ORR in the previously treated group was 63% (95% CI: 49%, 76%) and median DoR was 12.6 months (95% CI: 5.8, NE). In comparison, the ORR in the single-agent dabrafenib group was 27% (95% CI: 18%, 38%) and median DoR was 9.9 months.

The combination therapy showed a consistent safety profile with those of the individual agents. The most common adverse reactions included pyrexia, fatigue, nausea, vomiting, diarrhea, dry skin, decreased appetite, edema, rash, chills, hemorrhage, cough, and dyspnea. Lab abnormalities were also reported, with more common severe (Grade 3–4) abnormalities being hyponatremia, lymphopenia, anemia, hyperglycemia and neutropenia, among others. Discontinuation rates of dabrafenib and trametinib were 18% and 19%, respectively.

Additionally, the FDA has approved the Oncomine Dx Target Test (Thermo Fisher Scientific), a next generation sequencing test designed to detect the presence of mutations associated with lung cancer such as BRAF, ROS1 and EGFR. The test aims to identify patients with the BRAF V600E mutation for eligibility for the combination therapy using a single sample of paraffin-embedded tumor (FFPE) tissue using the Ion PGM Dx System.

Both Tafinlar and Mekinist received initial approval in 2013 as single agents for the treatment of advanced or metastatic melanoma with BRAF V600E mutation. Tafinlar is available as 50mg and 75mg capsules in 120-count bottles. Mekinist is available as 0.5mg and 2mg film-coated tablets in 30-count bottles.

For more information visit Novartis.com.