When it comes to brain cancer treatment, personalized medicine approach is key and understanding who will benefit from new treatments and who should avoid them if they are going to have a bad side effect. And, immunotherapy is the forefront of novel therapy for patients with brain cancer. Scientists at Moffitt Cancer Center are working to understand how to turn on the immune system and focus it on the brain. Our researchers found that combination therapy with ipilumab and nivolumab in patients with brain metastases from melanoma was extremely effective in some patients. Many of whom are alive, doing extremely well and are enjoying life five years post treatment.
For the first time in decades, we could see what was possible in brain tumors and how effective treatments could be if we could just figure out the best treatment. It’s the little things like timing or sequencing. In our experiments with test tubes and mice, immunotherapies and targeted therapies such as BRAF MEK inhibitors are performing very well. Somehow the immunotherapy helped to first set the stage for targeted therapies to work better. "It is very helpful for us to understand the clinical setting and provide a direct and fast pipeline to bring these discoveries to the clinic to make a difference right away," said Dr. Peter Forsyth. We have several clinical trials to test these ideas in patients and determine the best approach to use.
In gliomas brain metastasis (GBM), using a single immune checkpoint inhibitor is probably not very effective and the reasons for this are not clear. Although it’s likely immunosuppressive cells in the tumor microenvironment that make a tumor "cold" and less likely to respond to the treatment. Dr. Solmaz Sahebjam, a medical oncologist and head of the Early Phase Drug Development Program at Moffitt Cancer Center, is tackling this problem head-on. "We know that using a single immunotherapy in GBMs is not going to be enough to attack and kill these tumors. Therefore, we are combing several immunotherapies approaches together. We think the early results are very exciting and are much better than expected,” said Dr. Sahebjam.
In a Phase I Trial of Hypofractionated Stereotactic Irradiation (HFSRT) Combined with Nivolumab, Ipilimumab and Bevacizumab in Patients with Recurrent High Grade Gliomasstudy (MCC18661), the study is to evaluate the safety and tolerability of nivolumab, given in combination with hypofractionated stereotactic re-irradiation of recurrent high-grade gliomas. Dr. Sahebjam is adding ipilimumab and nivolumab to two other treatments that work for recurrent GBM patients such as Avastin and Re-irradiation. Dr. Sahebjam found that the early results are very promising. People are living a lot longer than expected without any unexpected side effects.
While this is an early phase 1 study, she is optimistic that the treatment will be expanded into a larger, phase 2 study in a larger group of GMB patients. "I am treating some patients on this trial with Dr. Sahebjam and these patients do extremely well. We’re pleasantly surprised by the results. I’ve been a neuro medical oncologist for 25 years and it is great to see, finally, that we have much better treatments for GBM patients when their tumor recurs” said Dr. Peter Forsyth, medical oncologist and chair of Neuro-Oncology Department at Moffitt.
In a Phase I trial of Pembrolizumab and Vorinostat Combined with Temozolomide and Radiation Therapy for Newly Diagnosed Glioblastoma (MCC 19342), newly diagnosed GBM that are MGMT promoter methylated who, because the MGMT chemoresistance is silenced, have a better prognosis using combined immunotherapies. The treatment involves using Pembrolizumab with a HDAC check point inhibitor, Vorinostat. While this is also an early-phase study to enhance the immune response, the results are impressive.
Our neurosurgeon, Dr. Michael Vogelbaum is leading a study to examine the role of a special kind of cell in GBMs called a MDSC that gets into the tumor and keeps it "cold." "We think that these cells are really keeping GBMs 'cold and quiet' so that they are below the body's radar detection system. We are confident that we can find drugs to deliver into the GBM to silence these cells and allow the body’s own defense systems to finally recognize and kill the GBM cells," said Dr. Vogelbaum, MD, PhD, program leader and chief of neurosurgery of Neuro-Oncology.
"Seeing patients doing so well changed my life as well as the lives of patients. It’s amazing to bring together a group of world-renown scientists to develop novel therapies for brain cancer and see tremendous results," said Dr. Forsyth.