SALT LAKE CITY—The U.S. Food and Drug Administration announced on Oct. 27 that it has approved, for the first time, an oncolytic (cancer-killing) viral therapy in the United States. The drug was approved for use against late-stage melanoma, a deadly skin cancer that can be difficult to treat.
The approval came as the result of a recent Phase III study, which showed that more patients with late-stage melanoma, treated with a herpes cold sore virus designed to kill tumor cells, had a better response when compared to a different treatment. Robert Andtbacka, M.D., from Huntsman Cancer Institute at the University of Utah and Howard L. Kaufman, M.D., from Rutgers Cancer Institute of New Jersey, led the multisite study, published May 26 online in the Journal of Clinical Oncology.
"The goal of this targeted therapy is to treat late stage patients more effectively and with fewer side effects," says Andtbacka, associate professor of at the University's School of Medicine.
The researchers employed a genetically modified herpes virus, made by the pharmaceutical company Amgen, which was designed to replicate inside tumors and kill them. In addition, the virus contains a human gene to make granulocyte macrophage colony-stimulating factor (GM-CSF) with the goal of causing an anti-tumor immune response in the patient.
Frequently, tumor cells evade the immune system, but Andtbacka says the therapy was developed to retrain the immune system to recognize the melanoma as something that shouldn't be there. "Not only are the injected tumor cells destroyed, but the immune system is activated to fight the melanoma not only where we injected it, but also at distant sites."
In the clinical trial, patients with Stage IIIB, IIIC, or IV melanoma were randomized to receive either the virus therapy talimogene laherparepvec (T-VEC) injected directly into their tumors or to receive an injection of GM-CSF under the skin.
The researchers observed that T-VEC virus immunotherapy caused tumors to shrink compared to treatment with GM-CSF alone: 16 percent of T-VEC treated participants (n = 295) experienced a durable response, meaning that their tumors shrank for >6 months, relative to 2 percent of the GM-CSF alone group (n = 141). While patients' lifespans, on average, were only extended by a small amount (4.4 months), 32 (11 percent) of the T-VEC recipients and one GM-CSF recipient (<1 percent), showed no signs of cancer after treatment.
Both local and systemic immune responses after treatment with T-VEC were also observed by the researchers, supporting the idea that combining T-VEC with other immunotherapies might further increase effectiveness. Studies testing such combination therapies are currently underway.
Andtbacka says the most common adverse effects of the T-VEC treatment were modest, consisting of flu-like symptoms, such as fatigue, chills, nausea, and injection-site reactions. Although more severe adverse effects did occur in some patients, the only one occurring in > 2 percent of T-VEC treated patients was cellulitis, a potentially dangerous skin infection (2.1 percent). "This safety profile is encouraging, since this is the first randomized trial of an oncolytic virus in patients with cancer," says Andtbacka.
T-VEC represents a novel treatment option for patients with injectable metastatic melanoma. This collaborative work was enabled by Amgen, manufacturer of the T-VEC virus and will be marketed under the name IMLYGICTM.
FDA approves first-of-its-kind product for the treatment of melanoma: http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm469571.htm
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About at the University of Utah
Huntsman Cancer Institute (HCI) is one of the world's top academic research and cancer treatment centers. HCI manages the — the largest genetic database in the world, with more than 16 million records linked to genealogies, health records, and vital statistics. Using this data, HCI researchers have identified cancer-causing genes, including the genes responsible for melanoma, colon and breast cancer, and paraganglioma. HCI is a member of the (a 26-member alliance of the world's leading cancer centers) and is a National Cancer Institute-Designated Comprehensive Cancer Center. HCI treats patients with all forms of cancer and operates several high-risk clinics that focus on melanoma and breast, colon, and pancreas cancers. The HCI Cancer Learning Center for patient and public education contains one of the nation's largest collections of cancer-related publications. The institute is named after Jon M. Huntsman, a Utah philanthropist, industrialist, and cancer survivor.