Vaccine Gives Hope Against Advanced Melanoma

CCH Newsletter - 8/03/09

Patients with advanced melanoma, one of the most dangerous cancers, showed improved response to treatment and length of progression-free survival when a vaccine was added to their treatment with the immunotherapy drug interleukin-2 (IL-2).

Results from the Phase III clinical trial – the first of its kind in melanoma and one of the first in any type of cancer – were presented by M. D. Anderson researchers at the American Society of Clinical Oncology (ASCO) annual meeting in May.

Significance of study

According to the American Cancer Society, the incidence of melanoma is growing quickly. In 2009, more than 68,720 people in the United States will be diagnosed with the disease, and 8,650 will die because of it. The five-year survival rate for melanoma that has metastasized (spread to other parts of the body) is 16%.

"Obviously, this disease is in need of better therapies," says Patrick Hwu, M.D., professor and chair of M. D. Anderson's Department of Melanoma Medical Oncology and a co-investigator on the study.

Background

The peptide vaccine, known as gp100:209-217 (200M), works by stimulating patients’ T cells, which help control immune responses.

"This vaccine activates the body's cytotoxic T cells to recognize antigens on the surface of the tumor,” Hwu says. “The T cells then secrete enzymes that poke holes in the tumor cell's membrane, causing it to disintegrate."

A previous Phase II study combining the vaccine with IL-2 showed response rates of 42% in metastatic melanoma patients.

Conducting a large, multi-institutional trial with IL-2 is challenging because not all cancer centers and community hospitals can administer it. A highly specialized therapy, it may have significant side effects including low blood pressure and capillary leak syndrome, which pose risks to the heart and lungs. It often is delivered in intensive care units.

Research methods

This study, which started more than 10 years ago, included 185 patients at 21 centers across the country.

All participants:

Had advanced metastatic melanoma
Tested positive for cutaneous metastasis, an indicator of response to IL-2

In the study:

93 patients were treated with high dose IL-2
86 patients were treated with IL-2 and vaccine

Primary results

In the patients who received the vaccine:

22% had a significant response
Median time of progression-free survival was almost three months

In the patients who did not receive the vaccine:

10% had a significant response
Median time of progression-free survival was 1.6 months

Additional results

The median overall survival for patients who received the vaccine was 17.6 months, compared to 12.8 months for patients who received IL-2 only.

What’s next?

Hwu says more research with the vaccine is needed, including long-term follow-up of the Phase III patients. In addition, he says it is necessary to expand research to include more metastatic melanoma patients.

"While more follow-up is needed, this study serves as a proof-of-principle for vaccines' role in melanoma and in cancer therapy overall,” he says. “If we can use the body's defense system to attack tumor cells, we provide a mechanism for ridding the body of cancer without destroying healthy tissue."

This article was adapted by Dawn Dorsey from an M. D. Anderson news release.

Vaccine Shows Therapeutic Promise Against Advanced Melanoma