Advances in Melanoma Research

By Meg Monday

Melanoma is a potentially fatal type of skin cancer that begins in the melanocytes, which are the cells that are responsible for skin color. The incidence rate of melanoma has been climbing steadily since the early 1970s. Of the more than 1 million new diagnoses of skin cancer each year, roughly 68,000 involve melanoma. Although melanoma can be successfully cured in its early stages, it is the most common fatal form of skin cancer, accounting for more than 79 percent of all skin cancer– related deaths. More than 8,000 people die of melanoma each year in the United States. Research developments in melanoma therapy are ongoing, and doctors specializing in the treatment of melanoma continue to make advances.

Lifestyle: The Good News and the Bad News

As with many cancer types, lifestyle behaviors can play a role in melanoma risk. Sun safety is an obvious step to take to help decrease the risk of developing melanoma, but a few recent studies point to some additional lifestyle factors you may not have considered that are the subject of melanoma-related research.

  • According to a study by the US National Institutes of Health and AARP and published in the Journal of the National Cancer Institute, coffee drinkers are less likely to develop malignant melanoma, and their risk decreases with every cup they drink.1The research found that people who drank the most coffee every day enjoyed a lower risk of melanoma compared with those who drank little or no coffee. People who drank one to three cups a day had about a 10 percent decreased risk of melanoma compared with those who drank none at all; those who drank four or more cups had a 20 percent decreased risk. It is important to understand that the study uncovered only an association between coffee consumption and the risk of developing melanoma; it does not prove a true cause-and-effect relationship but is certainly intriguing.
  • The results of a study published in JAMA Internal Medicine recently found that men who take Viagra® (sildenafil) are 84 percent more likely to develop melanoma than men who do not.2 The study included an analysis of 25,848 men who completed self-reported questionnaires regarding Viagra use and the incidence of skin cancer, including melanoma, squamous cell carcinoma (SCC), and basal cell carcinoma (BCC). The average age of men in the study was 65, and about 6 percent had taken Viagra to treat erectile dysfunction.Recent Viagra use at baseline was significantly associated with an increased risk of melanoma; however, there was no increased risk of SCC or BCC. If men had ever used Viagra, they had double the risk of developing melanoma compared with those who never used the drug. This elevated risk remained even after adjusting for a family history of skin cancer, ultraviolet light exposure, other types of cancer, and more. The researchers concluded that Viagra may be associated with an increased risk of developing melanoma. More research is needed to establish a clear link. In the meantime men with a high risk of developing melanoma may want to use caution with Viagra, and physicians might want to screen for skin cancer prior to prescribing the drug.

Practice-Changing Results 

Several key developments are changing the landscape of melanoma treatment.

  • The first trial of the immunomodulator Yervoy® (ipilimumab) conducted in patients with Stage III melanoma appears promising, demonstrating an improvement by delaying cancer recurrence and improving survival.3
  • In metastatic melanoma both Opdivo® (nivolumab) and Keytruda® (pembrolizumab) were approved by the US Food and Drug Administration for the treatment of patients with unresectable or metastatic melanoma and disease progression following Yervoy and, if BRAF V600 mutation positive, a BRAF inhibitor.4
  • Opdivo and Keytruda belong to a new class of medicines called PD-1 inhibitors that have generated great excitement for their ability to help the immune system recognize and attack cancer. PD-1 is a protein that inhibits certain types of immune responses. Drugs that block PD-1 may enhance the ability of the immune system to fight cancer. Promising research was also published indicating that PD-1 inhibitors may be important as an initial therapy in advanced melanoma for individuals without a BRAF mutation, with Opdivo demonstrating a survival benefit when compared with chemotherapy as initial therapy.5
  • Research has also been focused on evaluating how to optimize the use of BRAF inhibitors. Certain gene mutations affect cancer behavior, and a large and growing number of targeted therapies have been proven effective against cancers that contain these mutations. Many advanced melanomas, for example, contain mutations in the BRAF gene and can be treated with drugs known as BRAF or MEK inhibitors. The BRAF gene is known to play a part in cell growth, and mutations in BRAF are common in several types of cancer. Approximately half of all melanomas carry a specific BRAF mutation known as V600E. This mutation produces an abnormal version of the BRAF protein that stimulates cancer growth. Researchers postulated that a combination of a BRAF inhibitor and a MEK inhibitor might mitigate the emergence of disease resistance that occurs with BRAF inhibition alone. Recent research has supported this, demonstrating improvement of duration of response and overall survival with the combination of two pathway inhibitors.6,7
  • In the age of personalized medicine, an important study by researchers at Memorial Sloan-Kettering Cancer Center represents the initial steps in understanding why some patients respond to Yervoy and others do not.8 About 80 percent of people with melanoma get little or no benefit from Yervoy, and this recent study demonstrated a correlation between number of mutations and Yervoy benefit. Although additional research is needed, this study is an important step toward a diagnostic test that would help determine which patients would benefit from Yervoy.

 

References 

  1. Loftfield E, Freedman N, Graubard B, et al. Coffee drinking and cutaneous melanoma risk in the NIH-AARP Diet and Health Study. Journal of the National Cancer Institute. 2015;107(2):1-9. doi: 10.1093/jnci/dju421.
  2. Li WQ, Qureshi AA, Robinson KC, Han J. Sildenafil use and increased risk of incident melanoma in US men: A prospective cohort study. JAMA Internal Medicine. 2014;174(6):964-70. doi:10.1001/jamainternmed.2014.594.
  3. Eggermont AM, Chiarion-Sileni V, Grob JJ, et al. Ipilimumab versus placebo after complete resection of Stage III melanoma: Initial efficacy and safety results from the EORTC 18071 Phase III trial. Journal of Clinical Oncology. 2014;32:5s. Abstract LBA9008.
  4. Ribas A, Hodi FS, Kefford R, et al. Efficacy and safety of the anti-PD-1 monoclonal antibody MK-3475 in 411 patients (pts) with melanoma (MEL). Journal of Clinical Oncology. 2014;32:5s. Abstract LBA9000.
  5. Robert C, Long GV, Brady B, et al. Nivolumab in previously untreated melanoma without BRAF mutation. New England Journal of Medicine. 2015;372:320-33. doi: 10.1056/NEJMoa1412082.
  6. Robert C, Karaszewska B, Schachter J, et al. COMBI-v: A randomised, open-label, phase III study comparing the combination of dabrafenib (D) and trametinib (T) with vemurafenib (V) as first-line therapy in patients (pts) with unresectable or metastatic BRAF V600E/K mutation-positive cutaneous melanoma. Paper presented at European Society for Medical Oncology Congress; September 26-30, 2014; Madrid, Spain. Abstract LBA4_PR.
  7. McArthur G, Ascierto P, Larkin J, et al. Phase 3, doubleblind, placebo-controlled study of vemurafenib versus vemurafenib + cobimetinib in previously untreated BRAFV600 mutation-positive patients with unresectable locally advanced or metastatic melanoma (NCT01689519). Paper presented at European Society for Medical Oncology Congress; September 26-30, 2014; Madrid, Spain. Abstract LBA5_PR.
  8. Snyder A, Makarov V, Merghoub T, et al. Genetic basis