National brain tumour research funding needs to increase to £35 million a year
Gene therapy shows promise and review of Phase 3 clinical trials from 2005-2022
Study could help explain why certain brain tumours don’t respond well to immunotherapy. A study led by researchers at the UCLA Jonsson Comprehensive Cancer Center has shed new light on why tumours that have spread to the brain from other parts of the body respond to immunotherapy while glioblastoma, an aggressive cancer that originates in the brain, does not.
In people with tumours that originated in other parts of the body but spread to the brain, treatment with a type of immunotherapy called immune checkpoint blockade appears to elicit a significant increase in both active and exhausted T cells (immune cells) — signs that the T cells have been triggered to fight the cancer. The reason the same thing doesn't occur in people with glioblastoma is that anti-tumour immune responses are best initiated in draining lymph nodes outside of the brain, and that process does not occur very effectively in glioblastoma cases.
Phase II Trial of Dabrafenib Plus Trametinib in Relapsed/Refractory BRAF V600–Mutant Pediatric High-Grade Glioma. BRAF V600 mutation is detected in 5%-10% of paediatric high-grade gliomas (pHGGs), and effective treatments are limited. In previous trials, dabrafenib as monotherapy or in combination with trametinib demonstrated activity in children and adults with relapsed BRAF V600–mutant HGG or tumours that have stopped responding to standard treatment (refractory).
This phase 2 trial of dabrafenib plus trametinib improved overall response rate versus previous trials of chemotherapy in molecularly unselected patients with pHGG. It was associated with durable responses and encouraging survival. These findings suggest that dabrafenib plus trametinib is a promising targeted therapy option for children and adolescents with relapsed/refractory BRAF V600–mutant HGG.
Brain Tumour Gene Therapy Shows Early Promise in First-in-Human Trial. In this study, researchers combined two gene therapies previously shown to be effective in animal models to evaluate its safety and efficacy in a small number of glioma patients. The researchers tested a combination of genetic therapies centred around two proteins – HSV1-TK and Flt3L. HSV1-TK is an enzyme that activates the antiviral drug valacyclovir – allowing the drug to kill dividing cells like those found in high-grade gliomas – while Flt3L is a cytokine and growth factor that recruits immune cells (typically absent from the brain) to kickstart the anti-cancer immune response.
The authors note that, although the study (published in The Lancet Oncology) was not sufficiently powered to analyse survival, the observed median overall survival of 21.3 months is promising, given the historical figure of 14.6 months. Larger studies are required to investigate the possible effects on survival.
Are we providing best available care to newly diagnosed glioblastoma patients? - Systematic review of phase III trials in newly diagnosed glioblastoma 2005-2022. Glioblastoma is the most aggressive primary brain cancer with a poor prognosis. Despite numerous studies in the past 17 years, effective treatment options for glioblastoma remain limited. This study aimed to identify and compare phase III clinical trials from 2005 to 2022 for glioblastoma in terms of efficacy and baseline characteristics.
The analysis showed that the majority of trials did not result in a significant improvement in overall survival (OS). Among the trials included in this analysis, only the EORTC/NCIC (temozolomide), EF-14 (tumour treating fields), and CeTeG (temozolomide with lomustine) studies demonstrated a positive OS outcome in the younger cohort (below 60 years of age).
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