FDA Approves Cobimetinib in Combination With Vemurafenib for Advanced Melanoma
The U.S. Food and Drug Administration (FDA) approved cobimetinib (Cotellic) to be used in combination with vemurafenib (Zelboraf) to treat metastatic or unresectable melanoma, with the BRAF V600E or V600K mutation.
“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 in the FDA’s Center for Drug Evaluation and Research. “[This] approval provides a new targeted treatment that, when added to vemurafenib, demonstrates greater benefit than vemurafenib alone in patients with BRAF mutation–positive melanoma.”
Cobimetinib works by blocking the activity of the MEK enzyme, which is part of a larger signaling pathway. Cobimetinib prevents or slows cancer cell growth. Vemurafenib is a BRAF inhibitor that affects a different part of the same pathway and was approved in 2011 to treat patients with melanoma that has spread to other parts of the body or cannot be removed by surgery, whose tumors express the BRAF V600E mutation, as detected by an FDA-approved test. Health-care providers should confirm the presence of BRAF V600 E or V600K mutation in their patients’ tumor specimens using one of the available FDA-approved tests prior to starting treatment with cobimetinib in combination with vemurafenib.
Clinical Study Results
The safety and efficacy of cobimetinib taken in combination with vemurafenib were demonstrated in a randomized clinical study of 495 patients with previously untreated, BRAF V600 mutation–positive melanoma that is advanced or cannot be removed by surgery. All study participants received vemurafenib and were then randomly selected to also take either cobimetinib or a placebo.
On average, patients taking cobimetinib plus vemurafenib had a median progression-free survival of 12.3 months, compared to approximately 7.2 for those taking vemurafenib only. In addition, patients taking cobimetinib plus vemurafenib lived longer, with approximately 65% of patients alive 17 months after starting treatment as compared to half of those taking vemurafenib only. Additionally, 70% of those taking cobimetinib plus vemurafenib experienced complete or partial shrinkage of their tumors, compared to 50% among those taking vemurafenib plus placebo.
The most common side effects of treatment with cobimetinib in combination with vemurafenib are diarrhea, photosensitivity reaction, nausea, pyrexia, and vomiting.
Cobimetinib may cause severe side effects including cardiomyopathy, rhabdomyolysis, primary cutaneous malignancies, retinal detachment, severe skin rash, hepatotoxicity, hemorrhage, and severe skin rash due to photosensitivity. 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 final overall survival analysis from the coBRIM study will be presented at the Society for Melanoma Research (SMR) 2015 International Congress held in San Francisco, California from November 18-21.
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®.
