Findings related to the common anti-seizure and neuropathic pain drug offer new hope for extending life expectancy in patients with one of the deadliest forms of brain cancer.

A new study by investigators from Mass General Brigham suggests that gabapentin, a relatively common anti-seizure/pain medication, is linked to improved survival in patients with glioblastoma (GBM) — the most common and deadly form of brain cancer in adults.

The findings, published in Nature Communications, are based on a retrospective analysis and add new evidence to help patients with this devastating disease.

"This study is an exciting step forward," said lead author Joshua Bernstock, MD, PhD, a clinical fellow in the Department of Neurosurgery at Brigham and Women's Hospital, a founding member of the Mass General Brigham healthcare system.

"GBM is a relentlessly progressive and nearly universally fatal disease. The discovery that an already approved medication with a favorable safety profile can extend overall survival represents a meaningful and potentially practice-changing advance."

GBM is a highly aggressive and deadly form of brain cancer.

With about 12,000 new cases diagnosed annually in the United States, GBM accounts for most primary brain tumours in adults.

Overall survival has barely improved over the last several decades, with most patients living only 12 to 14 months after diagnosis and 5.5 months after recurrence.

The new study was sparked by insight from the field of cancer neuroscience.

This research area focuses on how tumours manipulate neural signalling to fuel their growth. 

A 2023 study published in Nature identified thrombospondin-1 (TSP-1)—a protein involved in neural circuit development and remodelling—as a key mediator of interactions between neurons and tumour cells that promote glioma growth. In mouse models, this neuron–tumour axis was successfully targeted using gabapentin, suggesting a potential therapeutic strategy.

Intrigued by this research, Bernstock and colleagues analysed the outcomes of 693 GBM patients at Mass General Brigham.

Many of the patients were already taking gabapentin for reasons that typically centered on nerve pain.

Those who were taking the drug survived an average of 16 months compared to 12 months for those who weren't.

This four-month survival benefit was statistically significant.

Because the results seemed “almost too good to be true,” according to Bernstock, he connected with Dr. Shawn Hervey-Jumper's team at University of California, San Francisco (UCSF) to add to the dataset and discovered they were able to replicate what was found at Mass General Brigham.

Of the 379 patients with newly diagnosed GBM included in the UCSF cohort, patients on gabapentin survived an average of 20.8 months, while those not taking gabapentin survived an average of 14.7 months.

Together, the data included 1,072 patients and found a significant survival benefit.

The study also found that patients treated with gabapentin had lower levels of serum TSP-1, suggesting that the protein may serve as an indicator of treatment response. However, the relationship between TSP-1 levels and gabapentin needs further investigation, Bernstock said.

"There have been very few advances in survival for GBM patients since the early 2000s," Bernstock said.

"We need to think more creatively about the emerging biology in these tumours and how to target them." 

While the findings are promising, the study is retrospective — the researchers didn't give patients gabapentin in a controlled way to test its effects. Bernstock stressed that larger, randomised clinical trials are needed to confirm the results and explore the role of gabapentin and TSP-1 in GBM progression.

Disclosures: Bernstock has an equity position in Treovir Inc. and UpFront Diagnostics. Bernstock is also a cofounder of Centile Bioscience and on the NeuroX1 and QV Bioelectronics scientific advisory boards.

Source: Mass General Brigham