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FDA Approves Two Drugs, Companion Diagnostic Test for Advanced Skin Cancer

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Key Points

  • Dabrafenib (Tafinlar), a BRAF inhibitor, is approved to treat patients with melanoma whose tumors express the BRAF V600E mutation.
  • Trametinib (Mekinist), a MEK inhibitor, is approved to treat patients whose tumors express the BRAF V600E or V600K gene mutations.
  • The approval of the THxID BRAF companion diagnostic test is based on data from clinical studies that support the dabrafenib and trametinib approvals.

The U.S. Food and Drug Administration today approved two new drugs, dabrafenib (Tafinlar) and trametinib (Mekinist), for patients with advanced or unresectable melanoma, the most dangerous type of skin cancer.

Dabrafenib, a BRAF inhibitor, is approved to treat patients with melanoma whose tumors express the BRAF V600E gene mutation. Trametinib, a MEK inhibitor, is approved to treat patients whose tumors express the BRAF V600E or V600K gene mutations. Approximately half of melanomas arising in the skin have a BRAF gene mutation. Dabrafenib and trametinib are being approved as single agents, not as a combination treatment.

The FDA approved dabrafenib and trametinib with a genetic test called the THxID BRAF test, a companion diagnostic that will help determine if a patient’s melanoma cells have the V600E or V600K mutation in the BRAF gene.

Targeting the Molecular Drivers of Melanoma

“Advancements in our understanding of the biologic pathways of a disease have allowed for the development of dabrafenib and trametinib, the third and fourth drugs the FDA has approved for treating metastatic melanoma in the past 2 years,” said Richard Pazdur, MD, Director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research.

Zelboraf (vemurafenib) and Yervoy (ipilimumab) were approved in 2011 for the treatment of metastatic or unresectable melanoma.

“The coapproval of dabrafenib and trametinib and the second companion diagnostic for BRAF mutation detection demonstrates the commitment of pharmaceutical and diagnostic partners to develop products that detect and target the molecular drivers of cancer,” said Alberto Gutierrez, PhD, Director of the Office of In Vitro Diagnostic Devices and Radiological Health in the FDA’s Center for Devices and Radiological Health.

The FDA’s approval of the THxID BRAF test is based on data from clinical studies that support the dabrafenib and trametinib approvals. Samples of patients’ melanoma tissue were collected to test for the mutation.

Dabrafenib Study

Dabrafenib was studied in 250 patients with BRAF V600E gene mutation–positive metastatic or unresectable melanoma. Patients were randomly assigned to receive dabrafenib or the chemotherapy drug dacarbazine. Patients who took dabrafenib had a delay in tumor growth that was 2.4 months later than those receiving dacarbazine.

The most serious side effects reported in patients receiving dabrafenib included an increased risk of skin cancer (cutaneous squamous cell carcinoma), fevers that may be complicated by hypotension, severe rigors, dehydration, kidney failure, and increased blood sugar levels requiring changes in diabetes medication or the need to start medicines to control diabetes.

The most common side effects reported in patients receiving dabrafenib included hyperkeratosis, headache, fever, joint pain, noncancerous skin tumors, hair loss, and hand-foot syndrome.

Trametinib Study

Trametinib was studied in 322 patients with metastatic or unresectable melanoma with the BRAF V600E or V600K gene mutation. Patients were randomly assigned to receive either trametinib or chemotherapy. Patients receiving trametinib had a delay in tumor growth that was 3.3 months later than those on chemotherapy. Patients who previously used dabrafenib or other inhibitors of BRAF did not appear to benefit from trametinib.

The most serious side effects reported in patients receiving trametinib included heart failure, lung inflammation, skin infections, and loss of vision. Common side effects included rash, diarrhea, peripheral edema, and skin breakouts that resemble acne.

Women of child-bearing years should be advised that dabrafenib and trametinib carry the potential to cause fetal harm. Men and women should also be advised that dabrafenib and trametinib carry the potential to cause infertility.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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