Yervoy Treatment for Melanoma

Posted on: February 15, 2013

February 2013

Good News For Melanoma Diagnosis

Diablo Valley Oncology

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Yervoy Treatment for Melanoma

Dr. Matthew SirottBy Matthew Sirott, MD

Medical Oncologist/Hematologist Melanoma, one of the most serious forms of skin cancer, is diagnosed in over 70,000 patients yearly in the US and causes 9000 deaths. The prognosis for patients with me- tastatic disease has been dismal. The only curative treatment, Interleukin 2, is toxic, requires multiple intensive care unit admissions, and has cure rates around 5% even when only carefully selected patients most likely to benefit (those with lymph node or lung disease only) are chosen. Other therapies, including chemotherapy, have some efficacy that is modest at best. However, the times, they are a-changin’!! Over the last few years, new exciting develop- ments in molecular and immu- nologic therapy have changed the treatment paradigm and resulted in many more successes. Ipilimumab (Yervoy) is a genetically engineered antibody directed against the CTLA-4 receptor on T lymphocytes which act as a brake on the immune system. Therefore, blocking the activity of the T cells by Ipilimumab turns on the immune system, resulting in very significant efficacy, with a near tripling of survival at 2 years. 10% of patients get a complete response (CR) and these patients do not seem to relapse (out to 5 years). This data is astounding, given the previous record of melanoma therapy. Ipilimumab has a serious toxicity profile and must be administered by physicians familiar with the drug and the potentially serious autoimmune side effects. Braf is an activating mutation present in 50% of melanomas. Zelboraf (Vemurafenib) is a potent inhibitor of braf and has been shown to be extremely active in braf mutated melanoma, with an improved progression free and overall survival of 4 months. Note that this is similar to the herceptin benefit in breast cancer and Avastin benefit in colorectal cancer. The response rate was ten times the standard chemo arm. Toxicity is relatively mild, except for the high rate of cutaneous malignancy, usually squamous cell cancer. Many other new drugs are in development and awaiting approval. Initial results with AntiPD -1 antibody are very exciting and published in the NEJM (2012;366(26):2443). The response rate in melanoma was 28%, with half of all responses lasting greater than a year in this pretreated population. The antibody was active in several other cancers, as well. Other areas of research include inhibition of the MEK pathway and blocking angiogenesis with drugs like Avastin. The future looks brighter for melanoma patients. We at DVO have developed the California Skin and Melanoma Center to foster expertise in the treatment of all skin cancers, including squamous cell, basal cell, melanoma and rare tumor types such as Merkle cell and skin lymphoma. We have brought together community physicians interested in the dermatologic, surgical, medical and radiation therapies of these patients. If you have appropriate patients please call us at 925-677-7287 or check us out on the web at www.calskincancer.com.

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