The U.S. Food and Drug Administration has approved Cotellic (cobimetinib) for use in combination with vemurafenib for the treatment of patients with advanced melanoma with a BRAF V600E or V600K mutation and that is metastatic and cannot be removed by surgery. Cotellic works by blocking the activity of the MEK enzyme to slow or prevent cancer cell growth.
"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," Richard Pazdur, MD, Director of the FDA's Office of Hematology and Oncology Products, said in a news release.
"The approval provides a new targeted treatment that, when added to vemurafenib, demonstrates greater benefit than vemurafenib alone in patients with BRAF mutation-positive melanoma."
Vemurafenib (marketed in the U.S. as Zelboraf) is a BRAF inhibitor that affects a different part of the same pathway and has previously been approved 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 gene mutation, as detected by an FDA approved test (OT 9/10/11 issue).
Safety and Efficacy
The safety and efficacy of Cotellic used in combination with vemurafenib were established in a randomized clinical trial of 495 patients with previously untreated, BRAF V600 mutation-positive melanoma that was advanced or could not be removed by surgery. All the patients received vemurafenib and were randomly selected to also take either Cotellic or a placebo.
The patients who received Cotellic plus vemurafenib had 12.3 months of progression-free survival, compared with 7.2 months for patients taking vemurafenib alone. Sixty-five percent of the patients who received Cotellic with vemurafenib were alive 17 months after starting treatment, compared with 50 percent of the patients taking vemurafenib alone.
And, 70 percent of those taking Cotellic plus vemurafenib experienced complete or partial shrinkage of their tumors, compared with 50 percent among those taking vemurafenib plus placebo.
The most common side effects reported for patients receiving Cotellic in combination with vemurafenib were diarrhea, photosensitivity reaction, nausea, pyrexia, and vomiting. Severe side effects reported for patients receiving the drug combination were cardiomyopathy, rhabdomyolysis, primary cutaneous malignancies, retinal detachment, severe skin rash, hepatoxicity, hemorrhage, and severe skin reaction due to photosensitivity.
People taking Cotellic are advised to avoid sun exposure, wear protective clothing, and use a broad spectrum ultraviolet A/ultraviolet B sunscreen to protect against sunburn; and women taking Cotellic should use effective contraception, since the medication can harm a developing fetus, the FDA noted.
Priority Review and Orphan Drug Designations
Cotellic was received under the FDA's priority review program, which provides an expedited six-month review of drugs that, at the time the application was submitted, have the potential to be a significant improvement in safety or effectiveness in the treatment of a serious condition. Cotellic also received Orphan Drug status, which provides incentives such as tax credits, user fee waivers, and eligibility for orphan drug exclusivity to assist and encourage the development of drugs for rare diseases.
Cotellic and Zelboraf are both marketed by Genentech.
Clinical Quick Facts: Cotellic
Drug: Cotellic (cometinib)
Approved Indication: Use in combination with vemurafenib for the treatment of patients with advanced melanoma with a BRAF V600E or V600K mutation and that is metastatic and cannot be removed by surgery
Serious Side Effects: Cardiomyopathy, rhabdomyolysis, primary cutaneous malignancies, retinal detachment, severe skin rash, hepatoxicity, hemorrhage, and severe skin reaction due to photosensitivity
Common Side Effects: Diarrhea, photosensitivity reaction, nausea, pyrexia, and vomiting