Glioblastoma Study Shows 50% Survival Rate After 5 Years

Author: Cedars-Sinai Medical Center
Published: 2013/11/25 - Updated: 2022/09/20
Contents: Summary - Main - Related Publications

Synopsis: The experimental treatment consists of a vaccine, ICT-107, intended to alert the immune system to the existence of cancer cells and activate a tumor-killing response. It targets six antigens involved in the development of glioblastoma cells. Targeting antigens highly expressed by cancer stem cells may be a viable strategy for treating patients with glioblastomas. Long-term disease remission was correlated with the expression of cancer stem cell tumor-associated antigens. With standard care, the median length of survival is 15 months after diagnosis of glioblastoma multiforme - and only 10% survive more than five years.

Glioblastoma

Glioblastoma, previously known as glioblastoma multiforme (GBM), is one of the most aggressive types of cancer that begin within the brain or spinal cord. Glioblastoma forms from cells called astrocytes that support nerve cells. Initially, signs and symptoms of glioblastoma are nonspecific. They may include headaches, personality changes, nausea, and symptoms similar to those of a stroke. Glioblastoma can occur at any age but tends to occur more often in older adults. Symptoms often worsen rapidly and may progress to unconsciousness.

Main Digest

Glioblastoma Multiforme is the most common and aggressive malignant primary brain tumor in humans, involving glial cells and accounting for 52% of all functional tissue brain tumor cases and 20% of all intracranial tumors. Common symptoms include seizure, nausea and vomiting, headache, and hemiparesis; the single most prevalent symptom is a progressive memory, personality, or neurological deficit due to temporal and frontal lobe involvement.

The kind of symptoms produced depends highly on the tumor's location, more so than on its pathological properties. Treatment can involve chemotherapy, radiation, and surgery. Median survival with standard-of-care radiation and chemotherapy with temozolomide is 15 months. Median survival without treatment is 41/2 months. Surgery is controversial because no randomized controlled trials have ever been done. Palliative treatment is usually conducted to improve quality of life and achieve longer survival. It includes surgery, radiation therapy, and chemotherapy. Supportive treatment focuses on relieving symptoms and improving the patient's neurologic function. The primary supportive agents are anticonvulsants and corticosteroids.

The Study

Eight of 16 patients participating in a study of an experimental immune system therapy directed against the most aggressive malignant brain tumors - glioblastoma multiforme - survived longer than five years after diagnosis, according to Cedars-Sinai researchers, who presented findings Nov. 23 at the Fourth Quadrennial Meeting of the World Federation of Neuro-Oncology.

Seven of the 16 participants still live, with survival lengths ranging from 60.7 to 82.7 months after diagnosis. Six patients were also "progression-free" for more than five years, meaning the tumors did not return or require more treatment. Four participants remain free of disease with good quality of life at lengths ranging from 65.1 to 82.7 months following diagnosis. One patient who remained free of brain cancer for five years died of leukemia.

The original clinical trial - a Phase I study designed to evaluate safety - included 16 patients with glioblastoma multiforme enrolled between May 2007 and January 2010 by researchers at Cedars-Sinai's Johnnie L. Cochran, Jr. Brain Tumor Center.

Results published in January at the end of the study showed a median overall survival of 38.4 months. Typically, when tumor-removal surgery is followed by standard care, which includes radiation and chemotherapy, the median length of survival is about 15 months. Median progression-free survival - the time from treatment to tumor recurrence - was 16.9 months at the study's end. With standard care, the median is about seven months.

The experimental treatment consists of a vaccine, ICT-107, intended to alert the immune system to cancer cells and activate a tumor-killing response. It targets six antigens involved in the development of glioblastoma cells.

According to information presented at the scientific meetings, all eight long-term survivors had tumors with at least five antigens, 75 percent had tumors with all six, and 100 percent had tumors with at least four antigens associated with cancer stem cells - cancer-originating cells that appear to enable tumors to resist radiation and chemotherapy and even regenerate after treatment.

"Our findings suggest that targeting antigens that are highly expressed by cancer stem cells may be a viable strategy for treating patients who have glioblastomas. Long-term remission of disease in this group of patients was correlated with the expression of cancer stem cell tumor-associated antigens," said Surasak Phuphanich, MD, director of the Neuro-Oncology Program at the Cochran Brain Tumor Center and professor of neurology with Cedars-Sinai's Department of Neurosurgery and Department of Neurology.

Based on the Phase I study results, the ICT-107 vaccine entered a Phase II multi-center, randomized, placebo-controlled trial in 2011.

The vaccine is based on dendritic cells, the immune system's most powerful antigen-presenting cells - those responsible for helping the immune system recognize invaders. They are derived from white blood cells taken from each participating patient in a routine blood draw. In the laboratory, the cells are cultured with synthetic peptides of the six antigens - essentially training the dendritic cells to recognize the tumor antigens as targets. When the "new" dendritic cells in the vaccine are injected under the patient's skin, they are intended to seek and destroy lingering tumor cells. The vaccine is administered three times at two-week intervals after standard radiation and chemotherapy.

Phuphanich is the first author of an abstract presented at the scientific meetings' poster session from 5 to 7 p.m. PST on Nov. 23.

ICT-107 is a product of the biotechnology company Immuno-Cellular Therapeutics, Ltd. Cedars-Sinai owns equity in the company, and Cedars-Sinai has exclusively licensed certain rights in the dendritic cell vaccine technology and related intellectual property to Immuno-Cellular Therapeutics, including rights associated with ICT-107, the vaccine investigated in this clinical study.

Disclosure:

Several research and presentation team members have ties to the company. Abstract co-author Keith Black, MD, a Cedars-Sinai physician, owns stock in the company. Senior author John Yu, MD, a Cedars-Sinai physician, owns stock in the company and is its founder, chief scientific officer, and chair of the board of directors. James Bender, Ph.D., MPH, a co-author, is Immuno-cellular Therapeutics' vice president for product development and manufacturing. Elma Hawkins, a co-author, also is identified with Immuno-cellular.

Co-authors

Co-authors who do not have relationships with the company include: Surasak Phuphanich, MD, Ph.D., first author; Christopher Wheeler, Ph.D.; Jeremy Rudnick, MD; Jethro Hu, MD; Mia Mazer; Hong Q. Wang; Miriam Nuno; Cherry Sanchez; Xuemo Fan; Jianfel Ji; and Ray Chu, MD.

Citation:

Abstract and poster presentation at Fourth Quadrennial Meeting of the World Federation of Neuro-Oncology, hosted by the Society for Neuro-Oncology, in San Francisco Nov. 21-24. Poster session from 5 to 7 p.m. PST Saturday, Nov. 23: "Long Term Remission Over 5 Years in Patients with Newly Diagnosed Glioblastoma (GBM) Treated with ICT-107 Vaccine: A Follow Up Study. "

Stopping Glioblastoma Brain Tumors

Attribution/Source(s):

This quality-reviewed publication pertaining to our Brain Cancers and Tumors section was selected for circulation by the editors of Disabled World due to its likely interest to our disability community readers. Though the content may have been edited for style, clarity, or length, the article "Glioblastoma Study Shows 50% Survival Rate After 5 Years" was originally written by Cedars-Sinai Medical Center, and submitted for publishing on 2013/11/25 (Edit Update: 2022/09/20). Should you require further information or clarification, Cedars-Sinai Medical Center can be contacted at the prpacific.com website. Disabled World makes no warranties or representations in connection therewith.

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