A new study has shed some light on the role of immunotherapy in glioblastoma. Glioblastoma remains a highly aggressive tumor with a median survival of approximately 14 months following treatment with surgery, chemotherapy and radiation. Novel therapies have been designed in an effort to improve outcomes in patients with Glioblastoma. Immunotherapy is one of such therapies designed to enhanced the ability of immune cells to seek out and destroy cancer cells. While this strategy has been quite effective for certain cancers such as melanoma and lung cancer, immunotherapy in glioblastoma has not been quite as effective.
It now appears that the timing of immunotherapy in glioblastoma is very critical. Prior attempts were based on initiating immunotherapy after surgical resection of the tumor mass through surgery. In the current study, patients whose immunotherapy was initiated prior to surgery had a survival that was doubled compared to those patients whose immunotherapy was initiated after surgery.
Patients with recurrent glioblastoma were randomly divided into two treatment groups depending on whether immunotherapy was initiated before or after surgery. Overall survival was doubled from 7.5 months to 15.6 months when immunotherapy was initiated prior to surgery. The authors also demonstrated that anti-tumor immune response was significantly enhanced when immunotherapy was initiated prior to surgery.
On an article in MedPage Today, the head Robert Prins, PhD, of UCLA Jonsson Comprehensive Cancer Center, and also an author of the study stated:
“Neoadjuvant immunotherapy is a very different situation than neoadjuvant chemotherapy. That’s designed to shrink the tumor to a margin where it can be taken out safely. Neoadjuvant immunotherapy actually serves as a primer to initiate the immune response, and then you can take out the bulk of this immunosuppressive tumor, and give more of continued immunotherapy that can sustain and enhance what was initially begun in the neoadjuvant setting.”
from Robert Prins, PhD, of UCLA Jonsson Comprehensive Cancer Center
“When you give PD-1 blockade — in this case pembrolizumab — before surgery in this setting, it can enhance the function of these T cells. When these T cells are activated with this blocking antibody they actually secrete these cytokines like interferon gamma that actually bind to the tumor cells, are internalized, and send a signal to them to stop dividing.
From the results at The National Center for Biotechnology Information, part of the US National Library of Medicine:
“These findings suggest that the neoadjuvant administration of PD-1 blockade enhances both the local and systemic antitumor immune response and may represent a more efficacious approach to the treatment of this uniformly lethal brain tumor.”
While these results are very exciting, it should be noted that this was a very small clinical study which was not designed to assess overall survival as a primary end-point. Hence larger studies are required in order to assess if these results apply at a larger scale.