When combined with a immunotherapy drug, researchers at the University of Texas M. D. Anderson Cancer Center claim that a vaccine for advanced melanoma shows improved response rates and progression-free survival for patients.
The findings, presented at the American Society of Clinical Oncology (ASCO), mark the first vaccine study in the disease - and one of the first in cancer overall - to show clinical benefit in a randomized Phase III clinical trial.
"Obviously, this is a disease, in its advanced setting, in need of better therapies for our patients," said Hwu, a co-investigator on the study.
"While more follow up is needed, this study serves as a proof-of-principle for vaccines' role in melanoma and in cancer therapy overall. If we can use the body's own defense system to attack tumor cells, we provide a mechanism for ridding the body of cancer without destroying healthy tissue," the expert added.
During their tenure at the National Cancer Institute (NCI), Hwu and Douglas Schwartzentruber, M.D., who is currently medical director of the Goshen Center for Cancer Care, were involved in the vaccine's development and early basic and clinical studies.
The peptide vaccine, known as gp100:209-217 (200M), works by stimulating patients' T cells, known for controlling immune responses.
"This vaccine activates the body's cytotoxic T cells to recognize antigens on the surface of the tumor. The T cells then secrete enzymes that poke holes in the tumor cell's membrane, causing it to disintegrate," explained Hwu.
After an NCI-led Phase II study combining the vaccine with Interleukin-2 (IL-2) showed response rates of 42 percent in metastatic melanoma patients, a Phase III randomized trial with the two agents opened more than a decade ago.
Conducting a large, multi-institutional trial with IL-2, however, had its own set of unique challenges, explained Hwu, as not all cancer centers and community hospitals are capable of administering the immunotherapy. A highly specialized therapy associated with such significant side effects as low blood pressure and capillary leak syndrome, which poses risks to the heart and lung, IL-2 is often delivered in intensive care units.
In the Phase III trial, 185 patients at 21 centers across the country were enrolled in the study. All had advanced metastatic melanoma and were stratified for cutaneous metastasis, a known indicator of response to IL-2. Patients were randomized to receive either high dose IL-2, or IL-2 and vaccine. In the IL-2 arm, 94 patients were enrolled and 93 were treated and evaluated for response; 91 were enrolled and 86 treated and evaluated in the IL-2 and vaccine arm.
The study found that those who received the vaccine had a significant response rate, 22.1 percent, and progression-free survival, 2.9 months, compared to 9.7 percent and 1.6 months respectively in those that did not. While not statistically significant, the median overall survival for those receiving vaccine trended positive, 17.6 months vs. 12.8 months.