FDA News

FDA approves Tafinlar plus Mekinist for BRAF V600E–mutant non–small cell lung cancer

The FDA approved use of dabrafenib in combination with trametinib for treatment of patients with metastatic non–small cell lung cancer whose tumors harbor BRAF V600E mutations, according to the agents’ manufacturer.

The combination of dabrafenib (Tafinlar, Novartis) — a BRAF inhibitor — and trametinib (Mekinist, Novartis), a MEK1/2 inhibitor — is the first targeted treatment approved in the United States specifically for patients with BRAF V600E–positive metastatic NSCLC.

“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, CEO of Novartis Oncology, said in a Novartis-issued press release. “Today's approval of [this] combination validates our expertise in tumor biology, which enabled us to develop the first targeted treatment for people with this rare mutation.”

The FDA also approved the Oncomine Dx Target Test (Thermo Fisher Scientific) to identify BRAF V600E mutations in eligible patients.

An estimated 1% to 3% of patients with NSCLC worldwide harbor BRAF mutations. BRAF V600E–positive tumors are particularly aggressive and contribute to poorer prognosis.

The FDA based its approval on results of a phase 2 multicenter, open-label, nonrandomized study that included 94 patients with stage IV BRAF V600E–positive NSCLC. Of these, 57 had received prior chemotherapy and 36 had treatment-naive disease.

Patients received 150 mg dabrafenib twice daily and 2 mg trametinib once daily.

Researchers reported overall response rates of 61% in the treatment-naive group and 63% in the previously treated group. Median duration of response was not estimable in the treatment-naive group and was 12.6 months in the previously treated group.

The most common adverse events included pyrexia, fatigue, nausea, vomiting, diarrhea, dry skin, decreased appetite, edema, rash, chills, hemorrhage, cough and dyspnea.

"The approval of Tafinlar [plus] Mekinist makes BRAF V600E the fourth actionable genomic biomarker in metastatic NSCLC, along with EGFR, ALK and ROS-1,” Bruce E. Johnson, MD, professor of medicine and chief clinical research officer at Dana-Farber Cancer Institute and Harvard Medical School, as well as president of ASCO, said in the release. “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.”

The FDA had granted breakthrough therapy designation to the dabrafenib–trametinib combination for treatment of patients with advanced or metastatic BRAF V600E–positive NSCLC who underwent prior treatment with chemotherapy.

The FDA previously approved the combination for treatment of patients with unresectable or metastatic melanoma who have BRAF V600E mutations.

The FDA approved use of dabrafenib in combination with trametinib for treatment of patients with metastatic non–small cell lung cancer whose tumors harbor BRAF V600E mutations, according to the agents’ manufacturer.

The combination of dabrafenib (Tafinlar, Novartis) — a BRAF inhibitor — and trametinib (Mekinist, Novartis), a MEK1/2 inhibitor — is the first targeted treatment approved in the United States specifically for patients with BRAF V600E–positive metastatic NSCLC.

“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, CEO of Novartis Oncology, said in a Novartis-issued press release. “Today's approval of [this] combination validates our expertise in tumor biology, which enabled us to develop the first targeted treatment for people with this rare mutation.”

The FDA also approved the Oncomine Dx Target Test (Thermo Fisher Scientific) to identify BRAF V600E mutations in eligible patients.

An estimated 1% to 3% of patients with NSCLC worldwide harbor BRAF mutations. BRAF V600E–positive tumors are particularly aggressive and contribute to poorer prognosis.

The FDA based its approval on results of a phase 2 multicenter, open-label, nonrandomized study that included 94 patients with stage IV BRAF V600E–positive NSCLC. Of these, 57 had received prior chemotherapy and 36 had treatment-naive disease.

Patients received 150 mg dabrafenib twice daily and 2 mg trametinib once daily.

Researchers reported overall response rates of 61% in the treatment-naive group and 63% in the previously treated group. Median duration of response was not estimable in the treatment-naive group and was 12.6 months in the previously treated group.

The most common adverse events included pyrexia, fatigue, nausea, vomiting, diarrhea, dry skin, decreased appetite, edema, rash, chills, hemorrhage, cough and dyspnea.

"The approval of Tafinlar [plus] Mekinist makes BRAF V600E the fourth actionable genomic biomarker in metastatic NSCLC, along with EGFR, ALK and ROS-1,” Bruce E. Johnson, MD, professor of medicine and chief clinical research officer at Dana-Farber Cancer Institute and Harvard Medical School, as well as president of ASCO, said in the release. “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.”

The FDA had granted breakthrough therapy designation to the dabrafenib–trametinib combination for treatment of patients with advanced or metastatic BRAF V600E–positive NSCLC who underwent prior treatment with chemotherapy.

The FDA previously approved the combination for treatment of patients with unresectable or metastatic melanoma who have BRAF V600E mutations.