Melanoma Vaccine Shows Promise in Trial
WEDNESDAY June 1, 2011 -- For patients with advanced melanoma, the most dangerous type of skin cancer, a vaccine combined with an immune-boosting drug is showing promise in a large clinical trial.
Therapeutic cancer vaccines, unlike typical vaccines that prevent infections, are meant to jump-start the immune system to help it battle existing tumors.
In this Phase 3 clinical trial, conducted at 21 care centers, researchers randomly assigned 185 patients with metastatic melanoma, meaning the cancer had spread, to either the vaccine followed by interleukin-2, a drug that activates the immune system, or interleukin-2 alone.
Those given the vaccine-drug combo showed more improvement than those given the drug alone, according to the study, which was published in the June 2 issue of the New England Journal of Medicine.
About 16 percent of those given the vaccine/interleukin-2 combination saw their tumors shrink by 50 percent or more, compared to 6 percent given interleukin-2 alone.
Those in the vaccine/drug group also had slightly longer "progression-free" survival -- 2.2 months compared to 1.6 months -- meaning they had more time in which the tumor didn't grow.
Patients given the combo also lived an average of nearly 7 months longer than those only give interleukin-2 -- nearly 18 months compared to about 11 months. While a "strong trend," those results were not statistically significant, said lead study author Dr. Douglas Schwartzentruber, medical director of the Goshen Center for Cancer Care at Indiana University Health.
"This is the first time that a vaccine has shown benefit in the treatment of patients with metastatic melanoma, and it's an early example of success with a cancer vaccine," Schwartzentruber said.
He and the other researchers reported that although the treatment-related toxic effects were similar in both groups, the vaccine "added some toxic effects" in the combination therapy group, including transient heart problems such as an abnormally rapid heart beat (tachycardia) and arrhythmias (15 percent vs. 2 percent).
In addition, the researchers reported one treatment-related death in the interleukin-2-only group and two such deaths in the combination therapy group.
Therapeutic vaccines are being studied for several types of cancers, with varying degrees of success, said William Chambers, director of clinical cancer research and immunology for the American Cancer Society.
In the melanoma trial, "they had a response. It wasn't a huge response, but clearly there was a fairly significant number that had a response," Chambers said. "And with this disease, there has not been a lot of success in treating these patients. The prognosis has been poor. They learned some significant lessons in this study."
In order for this vaccine to work, patients had to have a particular tissue type, called HLA-A2, which is present in about half of whites.
Last year, the U.S. Food and Drug Administration approved a vaccine to treat prostate cancer. Researchers at University of California, Los Angeles are also working on a vaccine to treat glioblastoma, the most aggressive type of malignant brain tumor.
The melanoma vaccine is based on a peptide, or a small portion of a protein, that's present on the surface of the melanoma cancer cells. Known as the gp100 peptide vaccine, the injection primes the immune system to recognize the protein, so that it then seeks out cells that produce the protein and destroys them.
The immune-boosting drug, interleukin-2, enhances the vaccine's effectiveness by stimulating the production of lymphocytes, a type of white blood cell that circulates throughout the body. More circulating lymphocytes means there are more cells available to do the job the vaccine has "educated" them to do, Schwartzentruber said.
The five-year survival rate for melanoma patients is less than 10 percent, experts said. Interleukin-2 is already FDA-approved to treat metastatic melanoma and kidney cancer.
The researchers said their next step is to improve the vaccine's efficacy. They hope by combining the vaccine with other agents (called adjuvants) or immune-boosting drugs, they might get a stronger response.
"We have now a strong proof of principal that with an immunological treatment we can see benefit, but at this point the benefits are small," Schwartzentruber said. "What we've decided to do is to try to develop a more potent vaccine before we do another trial."
The vaccine, if eventually approved by the FDA, would be relatively inexpensive because it is based on a protein that's present in most melanoma cancers, whereas other vaccines have had to be created for each individual patient, the researchers said.
The vaccine was developed at the U.S. National Cancer Institute, which also funded the study.
Posted: June 2011