How a combination of drugs can prevent melanoma recurrence
How a combination of drugs can prevent melanoma recurrence
Melanoma is a type of skin cancer that develops from the cells that control the pigment of the skin. It is caused by problems in these cells, called melanocytes, but the exact cause is unknown. Some factors that increase the risk of melanoma include exposure to UV rays, skin type, family history, and immune system weakness. Melanoma can be treated with surgery, chemotherapy, immunotherapy, targeted therapy, and radiation therapy1.
However, even after surgery, some patients with stage III melanoma, who have regional involvement at diagnosis, are at high risk of recurrence and death. Therefore, they may benefit from additional treatment after surgery, called adjuvant therapy, to reduce the chance of the cancer coming back.
One of the most promising adjuvant therapies for melanoma is a combination of two drugs that target a specific gene mutation that is found in about half of all melanomas. This mutation affects the BRAF gene, which makes a protein that helps the cells grow and divide. When the BRAF gene is mutated, it makes an abnormal protein that causes the cells to grow uncontrollably. This leads to the formation of tumors.
The two drugs that target this mutation are dabrafenib and trametinib. Dabrafenib is a BRAF inhibitor, which means it blocks the activity of the abnormal BRAF protein. Trametinib is a MEK inhibitor, which means it blocks another protein that works together with the BRAF protein in a pathway called MAPK. By blocking both proteins, dabrafenib and trametinib can stop the growth and spread of melanoma cells.
Dabrafenib and trametinib have been shown to improve survival in patients with advanced melanoma with BRAF mutations. But can they also prevent recurrence in patients with stage III melanoma who have had surgery?
A recent clinical trial called COMBI-AD answered this question2. In this trial, 870 patients with stage III melanoma with BRAF mutations were randomly assigned to receive either dabrafenib plus trametinib or placebo for 12 months after surgery. The primary outcome was relapse-free survival, which means the time until the cancer comes back or the patient dies.
The results were impressive. After a median follow-up of 2.8 years, the estimated 3-year rate of relapse-free survival was 58% in the dabrafenib plus trametinib group and 39% in the placebo group. This means that dabrafenib plus trametinib reduced the risk of relapse or death by 53%. The 3-year overall survival rate was also higher in the dabrafenib plus trametinib group than in the placebo group (86% vs. 77%). This means that dabrafenib plus trametinib reduced the risk of death by 43%.
The combination therapy was also effective in preventing distant metastasis, which means the spread of cancer to other organs. The 3-year rate of distant metastasis-free survival was 65% in the dabrafenib plus trametinib group and 47% in the placebo group. This means that dabrafenib plus trametinib reduced the risk of distant metastasis by 49%.
The safety profile of dabrafenib plus trametinib was consistent with what was observed in previous trials in patients with metastatic melanoma. The most common side effects were skin problems, fever, joint pain, fatigue, nausea, heart rhythm problems, liver problems, kidney failure, bleeding, and increased blood sugar levels. Some patients also developed new squamous cell skin cancers, which are usually less serious than melanoma and can be removed by surgery.
The authors of the trial concluded that adjuvant use of dabrafenib plus trametinib resulted in a significantly lower risk of recurrence in patients with stage III melanoma with BRAF mutations than placebo and was not associated with new toxic effects2. They also suggested that this combination therapy could become a new standard of care for these patients.
If you have melanoma that has spread beyond the skin, you should ask your doctor if your tumor has a BRAF mutation. If it does, you may be eligible for adjuvant treatment with dabrafenib plus trametinib after surgery. This could improve your chances of living longer and staying cancer-free.