FDA approves new treatment for late-stage skin cancer

FDA has approved ipilimumab (Yervoy, Bristol-Myers Squibb) to treat patients with late-stage (metastatic) melanoma, the most dangerous type of skin cancer.

Melanoma is the leading cause of death from skin disease. Figures from the National Cancer Institute indicate an estimated 68,130 new cases of melanoma were diagnosed in the United States during 2010 and approximately 8,700 people died from the disease.

The last therapeutic to be approved for melanoma, Interleukin-2, benefits only 10% to 15% of those with advanced melanoma, according to the Melanoma Research Foundation (MRF).

“Approval by FDA of Yervoy [ipilimumab] to treat patients with late-stage melanoma, the most dangerous type of skin cancer, illustrates the focus in R&D on morespecific indications in areas of clinical need,” Randy Vogenberg, PhD, principal at the Institute for Integrated Healthcare in Sharon, Mass., and executive director of the Biologic Access & Finance program at The Jefferson School of Population Health in Philadelphia, told Formulary.“Melanoma has been emerging in diagnosis and treatment as Baby Boomers, Gen X and Yers are aging afteryears of enjoying sun at the beach or backyard pool. This is not only life threatening, but represents another example like smoking cessation of altering lifestyles for future generations while having to treat expensiveillness in today’s population,” added Vogenberg, who is also author of Pharmacy Benefits: Plan Design and Management.

“Late-stage melanoma is devastating, with very few treatment options for patients, none of which previously prolonged a patient's life,” said Richard Pazdur, MD, director of the Office of Oncology Drug Products in FDA's Center for Drug Evaluation and Research. “Yervoy is the first therapy approved by the FDA to clearly demonstrate that patients with metastatic melanoma live longer by taking this treatment.”

Yervoy is a monoclonal antibody that blocks a molecule known as cytotoxic T-lymphocyte antigen or CTLA-4. CTLA-4 may play a role in slowing down or turning off the body’s immune system, affecting its ability to fight off cancerous cells. Yervoy works by allowing the body's immune system to recognize, target, and attack cells in melanoma tumors. The drug is administered intravenously.

Yervoy's safety and effectiveness were established in a single international study of 676 patients with melanoma. All patients in the study had stopped responding to other FDA-approved or commonly used treatments for melanoma. In addition, participants had disease that had spread or that could not be surgically removed.

The study was designed to measure overall survival, the length of time from when this treatment started until a patient's death. The randomly assigned patients received Yervoy plus an experimental tumor vaccine called gp100, Yervoy alone, or the vaccine alone.

Those who received the combination of Yervoy plus the vaccine or Yervoy alone lived an average of approximately 10 months, while those who received only the experimental vaccine lived an average of 6.5 months.

Common side effects that can result from autoimmune reactions associated with Yervoy use include fatigue, diarrhea, skin rash, endocrine deficiencies (gland or hormone), and inflammation of the intestines. Severe-to-fatal autoimmune reactions were seen in 12.9% of patients treated with Yervoy. When severe side effects occurred, Yervoy was stopped and corticosteroid treatment was started. Not all patients responded to this treatment. Patients who did respond in some cases did not see any improvement for several weeks.

“This is a critical breakthrough for advanced-stage melanoma patients who have far too few approved treatment options available,” said Timothy J. Turnham, the executive director of the MRF, in a foundation press release. “Patients have been waiting for a life-changing innovation like this one and news of the approval has galvanized the patient community.”

“The FDA’s decision to approve Yervoy is an important step forward for melanoma patients, but the work isn’t done,” Turnham said. “Until all patients have an option that can treat or cure their disease, we need to redouble our efforts.” As with the advances that were made in the development of “drug cocktails” for patients with HIV/AIDS, most melanoma researchers agree that testing combination therapies, including using Yervoy, is the key to achieving significant strides for a broader spectrum of patients.

Due to the unusual and severe side effects associated with Yervoy, the therapy is being approved with a Risk Evaluation and Mitigation Strategy to inform healthcare professionals about these serious risks. A medication guide will also be provided to patients to inform them about the therapy's potential side effects.