therapy stimulating the immune system slows the recurrence of glioblastoma -
A multicenter team of researchers, led by Cedars-Sinai researchers Department of Neurosurgery, Cedars-Sinai Maxine Dunitz Neurosurgical Institute and Dana-Farber Cancer Institute in Boston, found in a Phase II clinical trial of systemic therapy that stimulating immune slowed recurrence of glioblastoma or GBM, the most common and deadly malignant brain tumor.
They will present their findings during an oral presentation on June 1 at the annual meeting of the American Society of Clinical Oncology in Chicago.
The study included 124 newly diagnosed patients at 25 clinical trial sites in two-thirds of US patients were treated with ICT-107, an experimental vaccine based system cells immune called dendritic cells that were exposed to six synthetic proteins, or antigens, known to be involved in GBM development. Immunization is intended to stimulate the immune system to detect and fight cancer cells. The remaining third of patients, the composition of a control group was injected with their own dendritic cells that are not exposed to tumor antigens. All patients also received standard care, including surgical removal of the tumor, chemotherapy and radiotherapy.
Of the 124 patients, 117 were able to participate according to the protocol study, which included four initial treatments with ICT-107 followed by periodic maintenance doses. The trial was designed to evaluate the statistics of overall survival and progression-free survival - the length of time between initial treatment and the recurrence of the tumor. Glioblastomas are so aggressive and resistant to treatment, they usually return in the months of surgical removal, despite standard treatments.
In the most recent test results, treatment increased median overall survival by two months in patients treated according to protocol. It did not reach statistical significance, in part, researchers believe, because the follow-up time was relatively short; 45 patients remain alive for a new assessment. median progression-free survival, which increased three months in patients receiving treatment, was statistically significant.
"This trial had two major findings. First, the time until a patient's tumor grew by was significantly prolonged in patients who received the vaccine therapy. the quality of life of these patients was maintained longer and their performance score, and they needed steroids less frequently than unvaccinated patients. Secondly, we believe that the vaccine can be particularly beneficial for a group of patients with HLA-A2 type, suggesting that we move forward, there may be advantages to target this population, "said John Yu, MD, vice president of the department of neurosurgery, director of neuro-oncology surgery, medical Director of the brain tumor center and director of neurosurgery Gamma Knife program at Cedars-Sinai. He is the lead author of the abstract.
Among the subgroup analyzes, kind human lymphocyte antigen the study evaluated patients, whether HLA-A1 or HLA-A2. HLA classification is used to denote genetic related to immune cells. About 60 percent of people in the trial, as in the general population, were identified as HLA-A2 patients. The researchers said that the HLA-A2 patients treated with ICT-107 appear to have increased overall survival compared to those with HLA-A1
One analysis of key subgroups focused on changes of a gene -. O-6-DNA methyltransferase or MGMT methylguanine- - which can affect the patient's response to treatment. glioblastoma cells with MGMT "methylated" tend to be less sensitive to chemotherapy and radiation than those "methylated."
In patients with HLA-A2 and unmethylated MGMT, those in the control group had a median overall survival of approximately 12 months, compared to about 16 months in the treatment group. The improved median progression-free survival of 4.5 months for about six months in the control group at about 10.5 months among patients treated.
In patients with HLA-A2 and MGMT methylated or the control group or the treatment group reached a midpoint of survival to date. However, the median progression-free survival was statistically significant, with about 8.6 months control group and the treatment group to 24.5 months -. An advantage of 16 months for the group ICT-107
"This is the first placebo-controlled, randomized study of a vaccine for glioblastoma to show a significant advantage in a clinically meaningful endpoint, progression free survival . Furthermore, the subgroup of patients with MGMT promoter unmethylated and HLA-A2 seem to benefit particularly, "said Patrick Y. Wen, MD, director of the Center for neuro-oncology at the Dana cancer Institute -Farber and Professor of neurology, Harvard Medical School, who presented the data at the conference. It is first author of the abstract.
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