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Melanoma can be a potentially fatal skin cancer, especially when the disease is aggressive due to gene mutations. Many first-line therapies exist for treating this cancer, but no studies were done to compare the available treatments options.

Cutaneous melanoma is a deadly and aggressive form of skin cancer that accounts for over 3% of new cancer cases each year and has a staggering 15% mortality rate. When distant metastasis occurs, melanoma is generally regarded as incurable and the five-year survival rate is less than 10%.

In the early stages of the disease, melanoma is often managed with surgical excision alone. Patients who are diagnosed in later on stages of this disease, though, are not candidates for surgery and have to be managed with drug therapy.

Between 40-60% of melanomas undergo a mutation in the BRAF gene (an oncogene that when it mutates causes normal cells to become cancerous), and a number of competent treatment options are available for patients with these advanced BRAF-mutated melanomas. These treatment options include two classes of drug therapies, namely: targeted therapy such as chemotherapy, which causes tumour cells to stop growing and spreading, and immunotherapy which stimulates the immune system to attack cancer cells.

There are numerous effective first-line systemic treatment options available for patients diagnosed with advanced BRAF-mutated melanomas, but there were no clinical studies done to compare targeted treatments and immunotherapies. Therefore, a study was conducted to determine what the optimal initial treatment would be to offer the best possible outcome to patients diagnosed with these aggressive BRAF-mutated melanomas.

The study

The aim of the study was to evaluate the safety and efficacy of targeted treatments compared to immunotherapies for those patients who were diagnosed with aggressive BRAF-mutated melanoma, but who had not received any treatment yet.

The researchers analyzed 15 randomised controlled studies, that were published from 2011 to 2015, which assessed the benefits and adverse effects of targeted or immunotherapies in nearly 7,000 patients where surgery was not an option and where the cancer had spread to the lymph nodes, or who were diagnosed with distant metastatic disease.

The findings

The following discoveries were made once the information was analyzed:

  • A combination of MEK and BRAF targeted treatment and PD-1 immunotherapy were both equally sufficient in improving overall patient survival. The combination of these treatments was discovered to offer the best survival rate in patients with the aggressive melanoma and where quick action was required.

  • Combined MEK and BRAF treatment was the most effective therapy in improving survival that was progression-free.

  • Treatment with PD-1 immunotherapy was shown to be associated with a decreased risk of the occurrence of life-threatening events. The conclusion therefore was that the safety of PD-1 immunotherapy supported the use of this medication as first-line treatment in patients diagnosed with aggressive melanoma where quick action was not a priority.

In summary, treating patients who are newly diagnosed with BRAF-mutated melanoma, with a combination of immunotherapy options, decreases the risk of life-threatening events and improves their survival rate.

The clinical significance

The findings of this study will call for more research to be conducted on combination therapies for aggressive cancers in general. In the meantime, physicians should be aware that there are combination treatment options available to adequately manage newly diagnosed patients with aggressive melanoma, whether these patients require a quick action or not.

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