Cotellic/Zelboraf Combo Approved for Melanoma


The United States Food and Drug Administration (FDA) has approved Cotellic® (cobimetinib), to be used in combination with Zelboraf® (vemurafenib), for the treatment of melanoma that has spread from its site of origin, or is not able to be surgically removed. Patients must also have cancers that express either the BRAF V600 E or BRAF V600 K mutation, as ascertained by approved laboratory tests.

Melanoma is the most aggressive form of skin cancer, and often starts in the form of a mole. If detected and treated early, prior to spread, melanoma can be surgically removed. However, once melanoma has spread from its site of origin, particularly if it spreads to several distant sites in the body, it is difficult to cure with standard treatment options.

Fortunately, several new types of agents to treat melanoma have recently been approved, and have improved outcomes for patients with advanced melanoma. Targeted agents and immune stimulating agents have proven to be more effective than chemotherapy and radiation therapy in the treatment of this disease.

Both vemurafenib and cobimetinib target the same pathway in cells that is involved in cellular growth and replication. Abnormal activity within this pathway is implicated in the development of cancer. Each agent targets a different location within the same pathway, increasing the anti-cancer effects.

Vemurafenib was approved for the treatment of melanoma in 2011. Its approval is indicated for treatment of melanoma that had spread from its site of origin, and cannot be surgically removed. The cancer must express a gene mutation called BRAF V600E. This gene mutation is detected by an FDA approved laboratory test.

This is the first approval for cobimetinib, which blocks the activity of an enzyme known as MEK. Its approval is indicated for use with vemurafenib among patients with melanoma that has spread from its site of origin among patients whose cancers express BRAF V600 E or V600K.

The trial leading to the approval of cobimetrinib included 495 patients with previously untreated melanoma that has spread from its site of origin and/or could not be removed by surgery. All patients had a BRAF V600 mutation.

All patients were treated with vemurafenib. One group of patients was also treated with cobimetinib, while the other groups of patients received a placebo (inactive substitute such as a sugar pill).

  • A complete or partial shrinkage of cancer was achieved in 70% of patients treated with vemurafenib/cobimetinib, compared with only 50% of patients treated with vemurafenib/placebo.
  • The average time to cancer progression after starting treatment was approximately 12.3 months for patients treated with cobimetinib/vemurafenib, compared with 7.2 months for those treated with vemurafenib/placebo.
  • At 17 months after starting treatment, approximately 65% of patients treated with cobimetinib/vemurafenib were still alive, compared with approximately 50% of patients treated with vemurafenib/placebo.

Richard Pazdur, M.D., director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research stated that “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. Today’s approval provides a new targeted treatment that, when added to vemurafenib, demonstrates greater benefit than vemurafenib alone in patients with BRAF mutation-positive melanoma.”

Reference: United States Food and Drug Administration (FDA). FDA news release: FDA approves Cotellic as part of combination treatment for advanced melanoma. Available at: Accessed November 10, 2015.