FDA Approves Cobimetinib for Advanced Melanoma

November 11, 2015

The FDA has approved the MEK inhibitor cobimetinib in combination with the BRAF inhibitor vemurafenib for the treatment of advanced metastatic or unresectable BRAF-mutated melanoma.

The US Food and Drug Administration (FDA) has approved the MEK inhibitor cobimetinib (Cotellic) in combination with the BRAF inhibitor vemurafenib for the treatment of advanced metastatic or unresectable BRAF-mutated melanoma.

Cobimetinib was reviewed under the FDA’s priority review program designed for drugs that have the potential to provide significant improvements in the treatment of a serious condition.

The drug was approved based on efficacy and safety results from a phase III trial presented earlier this year at the 2015 American Society of Clinical Oncology Annual Meeting. The trial included 495 patients with treatment-naive BRAF V600–mutated metastatic melanoma. All patients were treated with the BRAF inhibitor vemurafenib and were then randomly assigned to cobimetinib or placebo.

With a median follow-up of 14 months, patients assigned to combination treatment with cobimetinib and vemurafenib had a progression-free survival of 12.3 months compared with 7.2 months for those on vemurafenib alone. In addition, patients assigned the combination had an overall response rate of 70% compared with 50% in patients on monotherapy.

The most common adverse events seen with cobimetinib/vemurafenib were diarrhea, photosensitivity reaction, nausea, pyrexia, and vomiting.

According to the FDA, cobimetinib may cause severe side effects including cardiomyopathy or rhabdomyolysis, primary cutaneous malignancies, retinal detachment, hepatotoxicity, hemorrhage, and severe skin rash due to increased sensitivity to sunlight. People taking cobimetinib should avoid sun exposure, wear protective clothing, and a broad spectrum ultraviolet A/ultraviolet B sunscreen to protect against sunburn. Women taking cobimetinib should use effective contraception, as the medication can cause harm to a developing fetus.

The FDA approved another MEK/BRAF inhibitor combination in January 2014. The MEK inhibitor trametinib and the BRAF inhibitor dabrafenib were approved to treat patients with metastatic or unresectable BRAF-mutated melanoma. A study of this combination showed that trametinib/dabrafenib resulted in an objective response rate of 76% compared with 54% in patients treated with the BRAF inhibitor alone.

“As we continue to advance our knowledge of tumor biology, we have learned that cancer cells have a remarkable ability to adapt and become resistant to targeted therapies. Combining two or more treatments addressing different cancer-causing targets may help to address this challenge,” said Richard Pazdur, MD, director of the Office of Hematology and Oncology Products at the FDA’s Center for Drug Evaluation and Research.