Vaccine for common, deadly brain tumour improves survival in some patients: study

Reported June 02, 2008

TORONTO - A vaccine aimed at ramping up the immune system to attack the most common and deadly type of brain tumour appears to significantly improve survival in a select group of patients, preliminary results from a small study suggest.

The vaccine works by targeting a specific protein found in some glioblastoma multiforme tumours (GBMs), boosting the body's immune response to kill malignant cells that express that protein and preventing regrowth of the cancer in patients already treated with standard surgery, chemotherapy and radiation.

"This vaccine represents a very promising therapy for a cancer that comes out of the blue and robs people of something most of us take for granted - time," Dr. John Sampson, a neurosurgeon at North Carolina's Duke University, said in a statement.

Sampson, who led the Phase 2 research, reported the study's findings at the American Society of Clinical Oncology (ASCO) meeting in Chicago on Monday.

The study was released the same day that U.S. Senator Ted Kennedy, 76, had surgery to remove a malignant glioma from his brain. Details about the exact type of Kennedy's tumour have not been disclosed, but some cancer specialists have speculated it might be a glioblastoma multiforme, based on his age. Other kinds are more common in younger people.

Sampson's study included 23 patients with GBMs, who went through standard therapy and then began receiving monthly injections of the vaccine - which targets a protein called EGFR (epithelial growth factor receptor) as well as a drug to enhance immune response.

Patients in the study survived without regrowth of their tumours for a median of 16.6 months, which more than doubles the usual 6.4-month expected progression-free survival in these patients, Sampson said.
 

As well, those who received the vaccine lived an average of 33 months, more than twice the average 14.3 months of all patients with GBMs treated with standard therapy.

"We're more than doubling survival time in this group, and we have some patients who are four, five or six years out from diagnosis, which is virtually unheard of in these people," said Sampson, who will be involved in the next phase of human testing, a multicentre trial that will include several sites in Canada.

Dr. James Perry, head of neurology at Sunnybrook Health Sciences in Toronto, said that although the preliminary results are exciting, they must be viewed in context.

Perry, chair of the Canadian Brain Tumour Consortium, said the 23 patients who received the vaccine tended to younger, under age 50, and had tumours that were located in a part of the brain that made them relatively easier to remove than patients with deeper tumours.

"If you take the patients that were selected, particularly in the patient trial, and then compare them to the overall statistics for glioblastoma, it looks very promising because the overall statistics include older patients, younger patients, patients who are doing well, patients who are doing poorly, some that get standard therapy, some that aren't able to," he said.

"So those sort of patients, we would have a survival expectation measured in years."

Beyond that, only about 30 per cent of people have GBMs that secrete the EGFR protein, he said. "So only a small proportion of patients with this disease will be eligible for this particular approach."

Still, Perry said the results are promising enough that the Canadian Brain Tumour Consortium (a network of experts and researchers) has recommended that Canadian patients be included in the next phase of vaccine testing.

Dr. Tom Davis, chief medical officer for Avant Immunotherapeutics Inc. of New Jersey, which holds the licence for the vaccine, said 26 sites in the United States and five in Canada have been chosen so far to test the efficacy of the therapy in a randomized controlled trial.

Davis said up to 375 patients could be enrolled in the study. That number would include an estimated 50 Canadians, Perry predicted.

But Perry stressed that while promising, the vaccine would not be for every patient diagnosed with glioblastoma.

Depending on the location, makeup of the tumour and other factors, the vaccine would apply to only about one in 10 patients
overall.

"So it isn't the answer to the disease, but our hope in the field is that it is the answer to ... this 10 per cent of the patients," he said. Once a proof of principle is established that such a vaccine works, "we can start to find out what are the unique attributes of those other nine out of 10 patients."

"But this is the first one, it's the one out of the gate," he said of the vaccine, "and hopefully if it proves to work, it would be a breakthrough therapy."

Sampson reported that the vaccine was well-tolerated by the 23 patients, with swelling at the injection site in the arm often being a patient's only complaint.

"The possibility of doubling expected survival - with few if any side-effects - would represent a big step and a lot of hope for this group of patients," he said.