The U.S. Food and Drug Administration (FDA) approved the combination therapy Tafinlar (dabrafenib) and Mekinist (trametinib) as a treatment for patients with metastatic non-small cell lung cancer (NSCLC) carrying specific mutations in the BRAF gene (namely V600E mutations).
Both drugs are developed and marketed by Novartis Pharmaceuticals. The combo treatment is the first therapy to become available in the U.S. for these patients, but has been available in Europe since March 2017.
“Patients with BRAF V600E mutation-positive metastatic NSCLC have responded less favorably to standard chemotherapy, suggesting that there is a critical need for a targeted therapy,” Bruno Strigini, Novartis Oncology’s CEO, said in a press release. “[The] approval of the Tafinlar + Mekinist combination validates our expertise in tumor biology, which enabled us to develop the first targeted treatment for people with this rare mutation.”
The approval by the FDA was based on the positive results that the Tafinlar and Mekinist combination showed in a Phase 2 open-label study (NCT01336634) in 93 patients with advanced NSCLC caused by BRAF V600E mutations. Thirty-six patients had never been treated before (treatment naïve patients), whereas 57 patients had received prior chemotherapy.
Results of the trial showed that Tafinlar (150 mg twice daily) and Mekinist (2 mg once daily) induced an overall response rate of 61 percent among treatment naïve patients and 63 percent among those who had received prior treatment.
The treatment was well-tolerated and safe. The most commonly reported side effects included fever, fatigue, nausea, vomiting, diarrhea, dry skin, decreased appetite, edema, rash, chills, hemorrhage, cough, and shortness of breath.
Further results will be presented at an upcoming medical meeting.
“The approval of Tafinlar + Mekinist makes BRAF V600E the fourth actionable genomic biomarker in metastatic NSCLC — along with EGFR, ALK and ROS-1,” said Bruce Johnson, an MD and researcher at the Dana-Farber Cancer Institute. “This is an important milestone for the lung cancer community as we are continuing to better understand the genomic drivers of cancer and develop effective treatments targeted for these biomarkers.”
Mutations in BRAF account for nearly 1 to 3 percent of all NSCLC cases in the world. Tumors expressing BRAF V600E mutations are more aggressive and lead to increased patient mortality. Diagnoses of patients with these mutations can be carried out with the Oncomine Dx Target Test, developed by the company Thermo Fisher Scientific.