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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.

Malignant Melanoma

Melanomas are malignant cancers that develop on the skin in the melanocyte cells where melanin (the pigment that gives skin its colour) is produced. Other areas where this cancer can develop are the eyes and, rarely, the intestines.

Causes

Melanomas will develop when an abnormality occurs in the melanocytes on the skin. Usually this can be attributed to DNA damage in cells which then grow out of control and form malignant masses.

The reason why this DNA damage occurs is not clearly understood, but the theory is that exposure to ultraviolet (UV) rays from the sun and tanning beds results in this problem. This theory still doesn't explain why melanomas can develop in areas of the skin that don't receive UV light exposure, so there may be a genetic link associated with these lesions.

Risk factors for the development of melanomas can include having a fair skin, recurrent sunburns and therefore UV light exposure, living closer to the equator, having many naevi/moles on the body and having a family history of melanomas.

Signs and symptoms

Melanomas can develop anywhere on the skin, but they usually occur on the sun exposed areas such as the arms, legs, face and back. This skin cancer can also develop in hidden areas such as the palms of the hands, in the fingernail beds and on the soles of the feet, and this usually occurs in people with darker skins.

People mistake normal naevi (moles) as being melanomas, but there is a way one can distinguish the difference and also know when a naevus starts becoming problematic, although melanomas can also develop by themselves without starting out as a normal naevus.

The ways to identify a melanoma is to look at the following aspects, think ABCDE, and if these changes do occur then it's suggested to consult with a healthcare practitioner as soon as possible:

  • Asymmetry - these skin lesions have an asymmetrical look to them, so one should try note if the two halves look different. 
  • Border - melanomas have irregular borders that can be scalloped or notched as well.
  • Colour - these lesions usually have multiple colours in them.
  • Diameter - look out for growth in a mole of more than 5 millimetres.
  • Evolving - a mole that grows in size or changes colour should be assessed further. Also, other signs such as an itching or bleeding lesion should make one suspicious for a melanoma.

Making the diagnosis

People with risk factors for developing melanomas should consult with their healthcare practitioners on a regular basis in order to undergo a head-to-toe exam so that any suspicious lesions can be addressed appropriately. Any changes in skin lesions or the development of new ones in these individuals should be noted and discussed with their doctors.

The diagnosis of melanoma is made by performing certain tests:

  • Punch biopsy -  a blade is pressed into the lesion and a round piece of skin is removed.
  • Excisional biopsy - the entire lesion or mole is removed together with a small border of normal skin.
  • Incisional biopsy - the most irregular part of the lesion or mole removed.

These specimens are then sent for analysis to determine if the lesion is a melanoma or not. If the diagnosis is confirmed, then it will be reported whether the entire melanoma was removed, what stage the cancer is and whether further treatment is necessary. 

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