Glioblastoma, considered one of the deadliest forms of cancer, claimed the life of Tragically Hip singer Gord Downie in 2017.Melissa Tait/The Globe and Mail
A new combination of treatments for glioblastoma allowed patients with the recurring brain cancer to live longer, and in some cases, shrank or even eradicated their tumours, researchers have found.
In a phase 1/2 trial, the international research team tested the use of oncolytic viruses, which specifically target and kill cancer cells, combined with a form of immunotherapy called an immune checkpoint inhibitor. This was the first study to use this combination of therapies in patients with recurrent glioblastoma. The results were published in Nature Medicine on Monday.
The treatment had a clinical benefit for more than half of the 49 participants, meaning their disease, which typically progresses, either remained stable or their tumour shrank. Overall, the median survival was 12.5 months, compared with the usual six to eight months. Three of the patients remain alive at 45, 48 and 60 months after treatment. The team, led by Toronto neurosurgeons, found no safety concerns with the treatment.
“This is what makes us really excited,” said lead author Farshad Nassiri, a senior neurosurgery resident at the University of Toronto. “There were a set of patients that had their tumour shrink quite considerably, and even in some patients, the tumour completely melted away.”
Glioblastoma is notoriously difficult to treat and is considered one of the deadliest forms of cancer. It claimed the life of Tragically Hip singer Gord Downie in 2017. The incidence of glioblastoma is estimated to be about four per 100,000 people in Canada. Patients typically have their tumours removed surgically, then receive chemotherapy and radiation therapy. But the cancer invariably recurs.
“Once the disease comes back, we essentially have no treatment options available for patients,” Dr. Nassiri said. Beyond managing symptoms, “there’s nothing that’s been shown to prolong patients’ survival.”
The novel therapy involves drilling a hole in the patient’s skull and inserting a tiny catheter with a fine copper tip into the centre of the tumour. Then, over the course of about an hour, the oncolytic virus is slowly injected. Afterward, the patient is intravenously given multiple doses of the immune checkpoint inhibitor, pembrolizumab.
The combination of the therapies targets the tumour in two ways, the researchers explained. While the virus can kill the tumour cells directly, it can also draw immune cells to the tumour. Tumours often evade attack from the immune system by expressing checkpoint proteins that prevent immune cells from working, Dr. Nassiri said. The immune checkpoint inhibitor blocks these proteins, so the tumour can no longer evade attack.
The trial involved patients at 13 hospitals across North America, including Toronto’s University Health Network. The researchers found that the patients generally tolerated the treatment well. While they reported some side effects, such as headache and fever, these were no different than expected for the normal patient population with recurrent glioblastoma, Dr. Nassiri said.
And patients did not develop new deficits in cognition or neurological function or additional complications, said senior author Gelareh Zadeh, who is the co-director of the Krembil Brain Institute at the University Health Network and a senior scientist at the Princess Margaret Cancer Centre.
“The people that we’ve seen survive actually had a good quality of life and functional status,” Dr. Zadeh said. “In other words, we’re not introducing a treatment just for the sake of prolonging life and then they have this really poor reaction that prevents them from functioning and enjoying life.”
Another key discovery of the study, she said, is an immune signature that can serve as a biomarker to predict a patient’s response to treatment. The researchers found that a certain balance of immune cells in the tumour and checkpoint proteins is likely needed for the therapy to work.
This balance “is the first description of a genetic signature, predicting response to immunotherapy in brain tumours,” Dr. Zadeh said.
In January, the journal Nature Reviews Clinical Oncology published a review article by a separate group of researchers that described several challenges to the development of oncolytic virus treatments, including regulatory hurdles related to the fact they are live, replicating viruses, and the need for careful storage and handling. However, it said oncolytic viruses offer immense promise as anti-cancer therapies.