News in Research on Glioblastoma in the Third Two-Months 2023
On time as usual, this is the twenty-first article of the project which aims to periodically (every two months) collect the news of research on possible treatments for glioblastoma multiforme.
Below are the news that we considered most significant. As with the previous articles in the series, each news item will be preceded by the original title with a link to the source and followed by a brief comment. The criterion with which news items are chosen is always to generally include only news relating to research in the clinical phase, unless the potential of research for the treatment of glioblastoma is truly remarkable.
Interstitial photodynamic therapy for newly diagnosed glioblastoma
The survival curves for this clinical study are very good and taking into account that the study involved patients with inoperable tumors makes the results even more interesting. The median progression-free survival (PFS) was 16.4 months, and the median overall survival was 28.0 months. 43.8% of patients had a PFS greater than 24 months. The 5-Ala, a dye is administered to the patient. The dye is absorbed by cancer cells much more than by normal cells. This dye is already used during surgery in order to make the tumor more easily visible to the surgeon. When the dye is excited by light (or by ultrasound when used with sonodynamic therapy), it kills the cells that absorb the dye. In this study, optical fibers were used to deliver light through a small hole in the skull. We still don’t have results related to sonodynamic therapy to understand which of the two ways works better. Sonodynamic therapy would have the advantage of being non-invasive while photodynamic therapy requires direct access to the area.
DCVax®-L: Mechanism of Action, Immunological Effects, and Clinical Trial External Controls Methodology
This presentation seeks to shed light on the results of the DCVax clinical trial for glioblastoma. In fact, the use of external control groups in the experimentation has been criticized by many. There have recently been several cases where long-term studies have not stratified by biomarkers that significantly influence outcomes. The aim of randomization should in fact be to distribute these different prognostic factors equally between the treatment and control groups. Using external control groups, we can account for every known prognostic indicator. Also, if a new prognostic factor is identified before the data are reported, we can recreate the external control group taking this new factor into account. This method, at least for serious and rare diseases such as glioblastoma in my humble opinion is also more ethical as we do not waste a patient’s life by administering only the placebo or the only standard of care that we actually know is not able to cure the illness. The presentation also explains well the mechanism of action of DCVax.
Vorasidenib first ‘game changer’ in 20 years for patients with IDH-mutant grade 2 glioma
This study shows that vorasidenib more than doubled the median progression-free survival time from 11 months to 27 months, and more than half of the patients are still alive, so median survival has not yet been calculated. This study focused on patients with mutated glioma. Vorasidenib is a targeted drug, designed to work specifically on patients with a mutation in IDH1 or IDH2. According to the new classification of brain tumors these tumors are not classified as glioblastomas. If the histological report indicates wild type IDH, it means that there are no IDH mutations.
Use of proton pump inhibitors (PPI) in glioblastoma (GBM) and relationship to overall survival in a national real-world evidence (RWE) database.
Dr. Castro hypothesized that the use of proton pump inhibitors (PPIs) may negatively impact the survival of patients with glioblastomas. Typically, testing such a hypothesis would be challenging and expensive. However, a comprehensive patient medication registry was used in this study. Analyzing these data it is possible to demonstrate a significant negative effect associated with the use of PPIs. This effect could potentially be as significant as the difference between methylated and unmethylated MGMT status. Proton pump inhibitors include Omeprazole (Prilosec), Esomeprazole (Nexium), Lansoprazole (Prevacid) Rabeprazole (AcipHex), Pantoprazole (Protonix), Dexlansoprazole (dexylante), and Zegerid (Omeprazole with sodium bicarbonate).
Targeting the IL4 receptor with MDNA55 in patients with recurrent glioblastoma: Results of a phase IIb trial
MDNA55 is a toxin targeting the interleukin 4 receptor (IL4R) that is overexpressed in GBM as well as tumor microenvironment cells. High IL4R expression is associated with poor clinical outcomes. MDNA55 was administered intratumorally as a single dose treatment. MDNA55 showed an acceptable safety profile in all evaluated patients (n = 44) with recurrent inoperable glioblastoma. Median survival was 11.64 months and OS-12 was 46%. A subgroup (n = 32) treated with high doses of MDNA55 showed the best benefit with 15-month mOS, OS-12 of 55%. Based on mRANO criteria, tumor control was observed in 81% (26/32), including those patients who exhibited pseudo-progression (15/26).
Powerful chemotherapy drug reaches brain tumors using novel ultrasound technology
This is the first study to quantify the effect of ultrasound-based blood-brain barrier opening on chemotherapy concentrations in the human brain. Opening the blood-brain barrier led to a four- to six-fold increase in drug concentrations in the brain. Scientists observed this increase with two different potent chemotherapy drugs, paclitaxel and carboplatin. This is also the first study to describe how quickly the blood-brain barrier closes after treatment with ultrasound technology. In most cases, the restoration of the blood-brain barrier occurs in the first 30-60 minutes.
That’s all for this issue on research news. Remember to register and enter your patient profile in Glioblastoma Navigator, the system is active and two video tutorials have been prepared. A Video Tutorial for Pazients and Caregivers and a Video Tutorial for Specialists (Doctors and Researchers).
Good luck and sincere wishes to all those who are fighting glioblastoma and their loved ones!