New melanoma treatment strategies continue to emerge | aad.org

New melanoma treatment strategies continue to emerge

               

By Terrence A. Cronin Jr., MD

Last Monday the Academy marked the 19th annual Melanoma Monday®. This year’s event is exciting both because of the strides we are making in raising awareness of this life-threatening disease as well as because of groundbreaking diagnostic and treatment developments that continue to emerge in our ongoing battle against melanoma.

Progress in battling this disease is the focus of the May issue of AAD’s Dialogues in Dermatology, of which I am humbly serving as editor. In preparing this edition I learned so much about these advances from our experts, who shared information on the latest progress in diagnosis, treatment, research, and prevention.

Diagnostic developments

When diagnosing melanoma, histopathologic examination remains the gold standard, demonstrating important information that will guide prognostication and treatment. Dr. Stuart Brown and Dr. Clay Cockerell discuss changes in the 2010 American Joint Commission on Cancer Guidelines for melanoma staging. These changes obviously are important for dermatopathologists to know, but anyone treating patients with melanoma — dermatologists, oncologists, and surgeons — also should understand them.  Lesion thickness has always been important for prognostication, but new criteria have given greater importance to mitotic figures and the presence or absence of ulceration.

Our experts also delve into how pathologists can search for specific markers when ambiguous lesions are sent for genotypic testing with fluorescent in situ hybridization (FISH), a test used increasingly in dermatopathology. This information can be used in conjunction with other factors to diagnose the lesion. 

In preparing this edition I learned so much about these advances from our experts, who shared information on the latest progress in diagnosis, treatment, research, and prevention.

Also discussed is the emergence of genetic testing as a major new tool that we hope will improve accuracy in diagnosing melanoma and more effectively targeting treatments.

Treatment advances

As researchers learn more about melanoma's molecular biology and host immunity, new treatment options are becoming available. Our May Dialogues also will feature Dr. Lynn Cornelius and Dr. Michael Heffernan discussing BRAF and MEK inhibitors, new targeted immunotherapeutic treatments aimed at blocking the MAP kinase pathway, which causes melanoma cells to propagate rapidly and take over. If these new treatments successfully halt the melanoma growth cycle, we can significantly improve the prognosis of patients being treated for melanoma.

Recently, the FDA approved vemurafenib, a selective BRAF inhibitor, for patients with inoperable melanoma or metastatic melanoma with the BRAF mutation.New treatments like vemurafenib are not perfect solutions, however. For example, only about 50 percent of patients have the BRAF mutation, and can benefit from treatment with vemurafenib. In addition, vemurafenib was shown to be very effective in patients in the short term, but melanoma eventually regained a foothold. These drugs also can cause a number of dermatologic side effects, which our experts discuss.

Another exciting area of exploration that our experts delve into is the use of a BRAF inhibitor to block the MAP kinase pathway and then a MEK inhibitor to prevent activation further along that same pathway. Oncologists across the country are investigating this approach, and this is the cutting edge of metastatic melanoma treatment.

Drs. Cornelius and Heffernan also discuss ipilimumab, an immunotherapeutic agent getting strong reviews. Ipilimumab is a monoclonal antibody targeting cytotoxic T-cell lymphocyte-4 (CTLA 4), which was approved by the U.S. Food and Drug Administration in 2011 to treat late-stage unresectable melanoma. Despite increased survival rates, ipilimumab may present potential life-threatening side effects and disease eventually may progress.

Despite their shortcomings, these medications certainly usher in a new era in melanoma understanding, offering hope to many patients who previously had none.

Prevention still key

When addressing skin cancer, prevention strategies are still critical in combatting this increasingly common disease. Clinicians continue to urge patients to apply sunscreen and avoid the sun. For patients who have already had skin cancer, dermatologists focus on measures to prevent disease progression.

Dr. Maryam Asgari and Dr. Maurice Thew discuss not only new paradigms for skin cancer prevention, but also a host of treatments for precancers and methods to prevent their progression to skin cancer. Dr. Asgari presents her insight into topical DNA repair treatments that have been shown to repair UV-induced pyrimidine dimers, which contribute to mutations, like T4N5 liposomal lotion.

This is all great information to discuss with your patients and colleagues. It is my hope that as research in the diagnosis and treatment of melanoma continues to advance, we will finally put an end to this dreaded disease. In the meantime, I encourage you to listen to the May issue of Dialogues in Dermatology and delve into the exciting progress we are making towards that goal.

Dr. Cronin is the editor-in-chief of Dialogues in Dermatology and a Mohs surgeon. Dialogues in Dermatology is a monthly audio subscription program that has been providing dermatologists with quality, cutting-edge medical information for more than 25 years.

Email the Member to Member editor at members@aad.org.

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References:

Balch CM et al. Final version of 2009 AJCC melanoma staging and classification. J Clin Oncol. 2009 Dec 20; 27(36):6199-6206.

Huang V, Hepper D, Anadkat M, Cornelius L. Cutaneous toxic effects associated with vemurafenib and inhibition of the BRAF pathway. Arch Dermatol. 2012 May; 148(5):628-33.

Chapman PB et al. Improved survival with vemurafenib in melanoma with BRAF V600E mutation. N Engl J Med 2011; 364:2507-2516.

Flaherty KT et al. Improved survival with MEK inhibition in BRAF-mutated melanoma. N Engl J Med 2012; 367:107-114.

DeBoyes T, Kouba D, Ozog D, Fincher E, Moy L, Iwata K, Moy R. Reduced number of actinic keratoses with topical application of DNA repair enzyme creams. J Drugs Dermatol 2010 Dec; 9(12):1519-1521.

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