In this interview, Dr. Grant-Kels discusses information presented at the American Academy of Dermatology (AAD) Summer Academy Meeting (July 31–August 4, 2013; New York, NY) regarding screening and therapy for melanoma.

PracticeUpdate: Dr. Grant-Kels, what is the most important new data concerning melanoma that you heard about at this year’s AAD summer meeting, and what do you think dermatologists should focus on?

Dr. Grant-Kels: First, I would like to credit to Dr. Allan Halpern from Memorial Sloan-Kettering Cancer Center because he very succinctly summarized the updates in melanoma, both for screening and therapy. He did an excellent job.¹

Melanoma screening

Dr. Halpern first talked about screening. To introduce the topic, he showed that—unlike prostate, breast, colorectal, and cervical cancers, in which mortality rates are dropping—the incidence of and mortality from melanoma continue to rise. He then discussed whether screening actually helps. This has been a controversial topic, despite the fact one would logically assume that, if we screen patients’ skin, we would detect skin cancers earlier and, therefore, mortality would be reduced. Some of the studies have not been confirmatory. However, a recent study done in Europe showed, unequivocally, that there was a reduced incidence of mortality from melanoma when screening was introduced.² Although screening can result in false positives and negatives, the bottom line is that screening patients’ skin does save lives.

Targeted therapies

Dr. Halpern then spoke about the most exciting area of melanoma, which are the new targeted therapies. There are two eras, if you will, for melanoma treatment: prior to 2011 and post 2011. Dr. Halpern recalled that, basically, only two approved treatments for metastatic melanoma existed prior to 2011. One was high-dose interleukin-2 and the other was a chemotherapy regimen known as DTIC, and both of these therapies had very low success rates and very high rates of side effects. Prior to 2011, metastatic melanoma was a devastating diagnosis.

Starting in 2011, improved understanding of the molecular pathways and the genetics involved in melanoma resulted in an improved understanding of the immunologic factors involved with its development and spread. The recognition that 50% of melanomas harbor oncogenic BRAF mutations at position V600was critical in the discovery of the drug vemurafenib. A significant number of patients with BRAF-mutated metastatic melanomas had a positive response to vemurafenib, which prolonged their lives. Unfortunately, the side effects from the drug were significant, even though most patients tolerated them relatively well. In particular, these patients developed others types of skin cancers, including squamous cell carcinomas and keratoacanthomas.

Finally, as recently as this year, the FDA approved two additional drugs after they were shown to be efficacious in patients with metastatic melanoma. One is dabrafenib, which is also a BRAF inhibitor, and the other is trametinib, which is a MEK inhibitor. So, it’s a very exciting time for those of us who take care of patients with metastatic melanomas because we now have three FDA-approved drugs that target specific sites in the molecular pathway.

Additionally, two other drugs are available to our patients with metastatic melanoma: ipilimumab, which was approved in 2011, and PDL1, which is still pending FDA approval. Ipilimumab is an immune stimulant and, therefore, helps the patient’s own immune system eradicate the melanoma. The anti-PDL1 antibody, which hopefully will be approved soon, has also been shown recently to result in tumor regression.³

We have now gone far beyond interleukin-2 and DTIC for patients with metastatic melanoma! I hope that, in the next update on melanoma therapy, these new drugs will be used in combination to reduce melanoma’s uncanny ability to outsmart new therapeutic options.

PracticeUpdate: Are dermatologists at the point where they are ordering genetic testing on patients with metastatic melanoma?

Dr. Grant-Kels: We do not routinely order serologic genetic testing on patients with melanoma, as is done in high-risk patients with breast cancer. Unlike high-risk patients who have mastectomies, we cannot remove someone’s skin. All we can do is monitor and check the skin frequently.

We do now routinely send tissue of patients with metastatic melanoma for testing to see if a BRAF mutation is present. That helps guide our choice of systemic therapy.

PracticeUpdate: Is there anything else new that dermatologists should be aware of relative to screening? And what about screening for patients who have already had melanomas removed?

Dr. Grant-Kels: Dermatologists have now embraced the use of the dermatoscope, which improves our diagnostic acumen. The other new advance is the FDA approval of some of the computer-assisted technologies to help us diagnose melanoma earlier. An example of this is MelaFind, a new technology now available in several dermatologic practices. In our department, this technology can help us decide which pigmented lesion to biopsy if we are unsure. Confocal microscopy is another exciting technology being used more frequently. We can use it in place of a skin biopsy as it allows us to see the skin on a cellular level. Hopefully, both of these new advances will help us diagnose skin cancers earlier and, ultimately, reduce the number of biopsies we need to perform.

PracticeUpdate: It is exciting that there will be a need for more screening of these patients since there will be more survivors than in the past.

Dr. Grant-Kels: Yes. Prior to 2011, most patients with metastatic melanoma died; so, this is very exciting! These new medications have revolutionized the treatment of melanoma!