Research News in the Third Two-Months of 2024

This is the twenty-sixth article of the project which aims to periodically (every two months) collect the latest research on possible treatments for glioblastoma multiforme. Below I list the news that we considered most significant to emerge in the last two months. As with previous articles in the series, each piece of news will be preceded by the original title with a link to the source and followed by a short comment. The criterion with which the news is chosen is always to generally include only news relating to research in the clinical phase, unless the potential of the research for the treatment of glioblastoma is truly remarkable.

Revolutionizing brain tumor treatment: the rise of AI in neuro-oncology
An article published in  npj Precision Oncology  highlighted the potential of Artificial Intelligence (AI) to revolutionize the management of brain tumors. The study illustrates how artificial intelligence techniques, such as machine learning and deep learning, can improve the diagnosis, treatment and prognosis of brain tumors, including glioblastoma. The authors suggest how AI can improve image accuracy, optimize workflows and provide comprehensive data analysis. Ethical and legal aspects are also discussed, as well as how patient-doctor relationships could benefit.

Long-term survivors of glioblastoma: Tumor molecular, clinical, and imaging findings
A study published in the Journal of Clinical Investigations highlighted factors that may predict or explain why long-term survivors (LTS) of glioblastoma live longer than their expected prognosis. Analyzing 23 LTS who lived three years or more after diagnosis, the researchers compared their data with that of short-term survivors (STS). The LTS group showed unique characteristics such as younger age at diagnosis, distinctive MRI features, and some genetic markers such as MGMT promoter methylation and TP53 mutations, often associated with better treatment responses. These findings highlight the variability of GBM prognosis and the importance of personalized therapeutic approaches based on detailed molecular and imaging analyses. The study supports the continued expansion of LTS registries to improve prognosis predictions and treatment strategies.

Ivy Brain Tumor Center announces Phase 0/2 clinical readout of niraparib indicating significant improvement in overall survival of newly diagnosed glioblastoma patients
The Ivy Brain Tumor Center at Barrow Neurological Institute announced results from its Phase 0/2 “trigger” trial of niraparib in people with newly diagnosed glioblastoma unmethylated for MGMT. These findings were presented at the American Society of Clinical Oncology (ASCO) annual meeting in Chicago, USA, this week. The study reported that the median overall survival (OS) was 20.3 months, nearly double the median OS observed historically with standard treatment in a similar patient population. A global pivotal Phase 3 clinical trial is expected soon to enroll 450 participants at more than 100 clinical sites in 11 countries around the world.

Medicenna Reports Significant Survival Benefit in Patients with Recurrent Glioblastoma Following Treatment with Bizaxofusp When Compared to a Matched External Control Arm at the 2024 ASCO Annual Meeting
Bizaxofusp (also known as MDNA55) is an immunotoxin that targets and kills cancer cells that express the interleukin-4 receptor (IL-4R), which is overexpressed in glioblastoma tumors. The latest evidence presented at the ASCO 2024 conference demonstrated that a single treatment of this drug, administered directly to the tumor site, led to a median overall survival of 13.5 months and a 12-month overall survival of 56.7% for patients with unresectable recurrent GBM. Additionally, patients who demonstrated tumor control (based on RANO 2.0 imaging criteria) after treatment had significantly improved median overall survival. Based on these results, a Phase 3 trial is in preparation.

No benefit from TMZ treatment in GB with truly unmethylated MGMT promoter: Reanalysis of the CE.6 and the pooled Nordic/NOA-08 trials in elderly GB patients
The methylation status of the MGMT promoter in glioblastoma is usually determined by molecular testing on tumor tissue samples, but testing methods and cutoff values ​​vary between institutions. This study reviewed data from previous clinical trials in elderly patients with glioblastoma using a rigorous definition of “unmethylated” (adding a safety margin below a major cutoff point to define the MGMT promoter as “truly unmethylated”) to determine the efficacy of temozolomide (TMZ). As expected, the results showed that patients with truly unmethylated MGMT promoter status did not benefit from TMZ. The study concludes that specific and validated methylation cutoffs should be applied in clinical trials and that better stratification of MGMT methylation status in clinical management will reduce toxicity without compromising patient outcomes.

Exhaustive in vitro evaluation of the 9-drug cocktail CUSP9 for treatment of glioblastoma
We have been following the developments of the CUSP9 protocol for some time which is an experimental approach for the treatment of relapsed glioblastoma that combines 9 repurposed drugs with continuous low doses of temozolomide (TMZ). We do this because in our opinion the cure for glioblastoma will come from a targeted combination of therapies. Although early studies demonstrated that the protocol can be administered safely under careful monitoring, researchers recently tested all partial combinations of the 9 drugs, in combination with TMZ, on two clonal cultures of glioma initiator cells from patient samples . The results showed that different partial combinations produce effects equivalent to the full protocol. This study highlights the importance and feasibility of personalized therapeutic approaches based on functional tests. If we administer fewer targeted and personalized drugs, the effect is the maximum achievable but the toxicity is reduced to a minimum. We are awaiting the phase 3 trial of this approach and this time we hope that Italian research institutes will also participate!

Before closing, for those interested, we would like to inform you that the financial statement for 2023, the accompanying report and related documents such as the statement for the 5×1000 have been included in the transparency section. Thanks to those who have helped us and continue to help us keep the volunteer organization alive. That’s all for this research news issue. Best of luck to all those who are fighting glioblastoma and their loved ones!