FDA Approves New Combo for Advanced Melanoma

Combination of Cotellic and Zelboraf shows superior overall and progression free survival in melanoma treatment.

The FDA today approved a new treatment option for patients with advanced melanoma.

Cobimetinib (Cotellic) was approved in combination with vemurafenib (Zelboraf) for the treatment of advanced melanoma that spread to other parts of the body or is unable to be removed via surgery, and has a specific abnormal BRAF, V600E, or V600K gene 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 2 or more treatments addressing different cancer-causing targets may help to address this challenge,” said Richard Pazdur, MD, director of the FDA Office of Hematology and Oncology Products in the Center for Drug Evaluation and Research. “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.”

Cotellic acts through blocking MEK enzyme activity as part of a larger signaling pathway. The drug is able to prevent or inhibit cancer cell growth.

Zelboraf was approved in 2011 as a BRAF inhibitor in patients with melanoma that spread to other parts of the body or can’t be removed by surgical resection, and with tumors expressing the BRAF V600E genetic mutation. Zelboraf treats a different section of the same signaling pathway affected by Cotellic.

The FDA stated that the presence of the BRAF V600E or V600K mutation should first be confirmed in tumor specimens prior to initiating treatment with Cotellic and Zelboraf.

The combination therapy was evaluated in a randomized clinical trial of 495 patients with previously untreated BRAF V600 mutation-positive melanoma that advanced or is not able to be removed by surgery.

All patients were administered vemurafenib and were randomly selected to also receive Cotellic or placebo.

Patients in the Cotellic plus vemurafenib treatment group showed a 12.3 month average delay in disease progression after starting treatment compared with approximately 7.2 months after starting treatment in the vemurafenib with placebo group.

Furthermore, patients in the Cotellic plus vemurafenib group had longer overall survival, as approximately 65% of patients were still alive after 17 months after starting treatment compared with 50% in the vemurafenib with placebo group.

Meanwhile, 70% of patients in the Cotellic plus vemurafenib group showed complete or partial tumor shrinkage compared with 50% in the vemurafenib plus placebo group.

The most common adverse events from the Cotellic with vemurafenib combination were diarrhea, sensitivity to ultraviolet light, nausea, fever, and vomiting.

Additionally, Cotellic may cause severe side effects, including cardiomyopathy, rhabdomyolysis, primary cutaneous malignancies, eye disease, severe skin rash, hepatotoxicity, hemorrhage, and severe skin rash from increased photosensitivity.

Patients treated with Cotellic should avoid sun exposure, wear protective clothing, and a broad spectrum ultraviolet A/ultraviolet B sunscreen, the FDA said. Furthermore, women administered Cotellic should use effective contraception because the drug can harm a developing fetus, according to the FDA.