Another Combination Targeted Therapy for Metastatic Lung Cancer  

The FDA approved encorafenib with binimetinib as a treatment for certain patients with non-small cell lung cancer. 

The U.S. Food and Drug Administration has approved encorafenib (Braftovi) with binimetinib (Mektovi) to treat adult patients with metastatic non-small cell lung cancer (NSCLC) whose tumors harbor a mutation in the BRAF gene called BRAF V600E. 

The mutation can be detected in the patients’ blood or in the tumor tissue by the FoundationOne Liquid CDx or FoundationOne CDx tests, respectively. These were included in the approval as companion diagnostics for encorafenib with binimetinib.  

Metastatic non-small cell lung cancer with tumors that have a mutation in the BRAF gene.

Encorafenib and binimetinib are molecularly targeted therapies that block the activity of BRAF and MEK, respectively. These proteins function in conjunction with each other within the same molecular pathway, which drives cell proliferation. BRAF inhibitors were developed as therapies for cancers driven by BRAF mutations. Simultaneous inhibition of BRAF and MEK is a strategy to prevent the development of resistance to BRAF inhibitors. The first combination of BRAF and MEK inhibitors (dabrafenib [Tafinlar] and trametinib [Mekinist]) for NSCLC was approved in 2017. 

The approval of encorafenib with binimetinib was based on results from PHAROS, an open-label, multicenter, single-arm, phase II clinical trial that assessed the combination therapy in patients with metastatic NSCLC with BRAF V600E mutations who had not been previously treated with BRAF or MEK inhibitors. Patients received encorafenib with binimetinib until disease progression or unacceptable toxicity. 

Among 59 patients who had not been treated with prior systemic therapy for their metastatic disease, the objective response rate (ORR) was 75%, and the median duration of response (DoR) was not estimable. Among 39 patients who had received prior treatment, the ORR was 46%, and the median DoR was 16.7 months. 

NSCLC is the most prevalent type of lung cancer. BRAF mutations are estimated to be present in 2% of NSCLC cases. According to federal statistics, it was estimated that 238,340 new lung cancer cases would be diagnosed, and 127,070 individuals would die of the disease in the United States in 2023. 

The FDA rendered its decision on October 11, 2023.