It is the the most lethal brain tumour of them all: glioblastoma multiforme (GBM) is a grade 4 astrocytoma with a global incidence of eight to nine cases per 100,000 people.
Glioblastoma multiforme is an incurable brain tumour that is also very aggressive. — AFP
GBM commonly affects men more than women. Although it affects people of all ages, it occurs most frequently in those aged between 55 to 60 years old.
It is also very hardy and constantly recurs despite the most aggressive treatments, rendering it incurable.
According to Hospital Universiti Sains Malaysia consultant neurosurgeon Professor Dr Zamzuri Idris, studies have shown that GBM patients on treatment have an average survival of 15 months at best, with only approximately one-fifth of patients surviving two years after diagnosis.
Hospital Sungai Buloh Neurosurgery Department head Datuk Dr Azmin Kass Rosman says that the current standard treatment consists of surgical removal of the brain tumour, followed by chemotherapy and radiotherapy.
The Stupp protocol, where the chemotherapy drug temozolamide is used with radiotherapy after surgery, has been adapted as the standard of care for treatment since its landmark introduction in 2005.
However, recent years have seen new breakthroughs in the cancer, especially in the understanding of glioblastoma biology, development of modern neurosurgery, improved radiotherapy options and the rapid advancements in immunotherapy.
Molecular checkpoints
Immunotherapy is a medical therapy designed to improve, supplement, or even replace conventional cancer treatments, in an attempt to reduce or remove cancerous growths by utilising the body’s natural defence mechanisms to fight off cancerous cells.
In fact, the 2018 Nobel Prize in Physiology or Medicine was awarded to James P. Allison and Tasuku Honjo for their work in describing this mechanism.
It is a very exciting field, and if it becomes viable, can hopefully help us to eradicate cancer.
Our immune system has the ability to discriminate between “self” (our own cells) and “non-self” (foreign cells) in order to protect the body against illnesses and infections caused by bacteria, viruses, fungi or parasites.
They can also eliminate unhealthy cells, including those that show signs of being cancerous.
In order to distinguish between healthy and unhealthy cells, our immune system is equipped with immune checkpoints, which can be the difference between cells living and dying.
When these immune checkpoints are hijacked by cancer cells, the immune system is “switched off”, allowing these cancer cells to gain the ability to disguise themselves and escape the checkpoint.
As the immune system now does not see these cells as unhealthy, it therefore allows them to multiply and the tumour grows.
For our immune system to identify these cancer cells as a problem and fight against them, it is crucial to remove these compromised immune checkpoints by using a checkpoint inhibitor.
By modulating the immune checkpoint’s activity via the checkpoint inhibitor, it is possible to harness our own immune system to act as an anti-cancer therapy.
Over the past few years, immunotherapy for GBM has gained wide interest.
The presence of the blood-brain barrier, which filters out many molecules, is the main challenge in GBM treatment.
However, studies have found that immune cells are capable of reaching brain tumours, making immunotherapy a viable treatment option.
Clinical development
Last year, the first randomised phase 3 clinical trial, CheckMate-143, of immune checkpoint inhibitor nivolumab was carried out to evaluate its efficacy and safety in patients with first recurrence of GBM.
However, it did not meet its primary endpoint of improved overall survival.
Several other immunotherapy treatments that showed promising results in early phase studies, had limited responses when observed in larger phase 3 clinical trials.
Meanwhile, a recent finding published in the journal Nature Medicine suggests that neoadjuvant administration (administration of therapeutic agents before a main treatment) of the checkpoint inhibitor enhances antitumour response and significantly extended overall survival of GBM patients.
This clinical trial may provide a way to extend survival in patients, alongside the use of chemotherapy, radiation or surgery.
Nevertheless, getting these GBM drugs to phase 3 trials is indeed a positive sign, seeing that it takes several years to even pass the phase 2 trials.
It is worth noting that clinical practice and laboratory studies are two different worlds.
Often, introducing new state-of-the-art treatment options into daily clinical practice is a gigantic task.
To date, immunotherapy is a promising field that holds boundless potential to succeed in areas where current therapies have not, but it is still necessary and crucial to acknowledge the capabilities and limitations of our resources and seek to understand the potential adverse effects of this new therapy.
Our ultimate aim would be to totally eradicate GBM not just by prolonging survival, but also by creating a meaningful and functional life for patients and their caregivers.
https://www.star2.com/health/2019/04/04/new-immunotherapy-aggressive-brain-tumour/
