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Season's greetings from the IBTA
All of us at the International Brain Tumour Alliance would like to take this opportunity to wish you a happy 2019. Our sincere thanks go to friends, funders, colleagues and others who are part of the international brain tumour community for the encouragement you have given us at the IBTA to continue working alongside you towards a better outcome for those affected by brain and CNS tumours. We hope that the next year’s developments in the world of neuro-oncology will bring us ever-closer to this goal.
Leading news
International Brain Tumour Awareness Week 2019 dates announced
Following the successes of 2018, the IBTA is delighted to announce that the next International Brain Tumour Awareness Week will be taking place from Saturday, 26 October to Saturday, 2 November 2019 inclusive. Read more about the IBTA’s awareness-raising initiatives on our website here.
Conference coverage and expert opinion on SNO 2018
PracticeUpdate has published a selection of opinion articles, videos, and news items covering the events of the 2018 Society for Neuro-Oncology Annual Meeting (SNO 2018), which was held in New Orleans, Louisiana, USA, on Nov 15 – 18, 2018. The IBTA was delighted to be exhibiting at and attending this important event, which featured announcements on many exciting research developments. Read more (free registration may be required to access some articles).
The US National Cancer Institute awards $4 million funding for adult and paediatric brain tumour sequencing projects
The National Cancer Institute (NCI) – the US government's principal agency for cancer research – has announced funding totalling $4 million for new adult and paediatric brain tumour research projects. The funding stems from recommendations made by a diverse group of stakeholders, comprising medical professionals, philanthropic and patient advocacy organisations (including Eliminate Cancer Initiative, the National Brain Tumor Society, American Brain Tumor Association, Pediatric Brain Tumor Foundation, and the IBTA), researchers, patients and others, who participated in the inaugural US Brain Cancer Mission Roundtable meeting in May 2018. The two community-driven projects that received the funding are GBM CARE (Cellular Analysis of Resistance and Evolution) and Project HOPE (High-Grade Glioma-Omics in Paediatric and AYA), which will both use single-cell sequencing technology to develop an in-depth understanding of the genomic, epigenomic, and immunological characteristics of individual adult glioblastoma tumours, and to capture critical information on tumour cell types and the tumour microenvironment that are missed by traditional sequencing techniques. Read more.
AUD $2.5 million grant awarded to COGNO to increase recruitment in brain tumour trials
The Cooperative Trials Group for Neuro-Oncology (COGNO) has been successful in achieving an AUD $2.5million grant from the Australian Brain Cancer Mission to improve treatments and outcomes for adults with brain cancer through increasing access to high quality international cancer clinical trials. The grant is over a 5-year period, and COGNO has established an International Clinical Research Sub-Committee to facilitate achievement of the grant objectives, which include opening more international trials in Australia and facilitating patient access to these trials. Read more (official Cancer Australia website).
Partnership between EORTC and Celgene for phase 3 trial of marizomib in newly diagnosed glioblastoma
EORTC, European Organization for Research and Treatment of Cancer, in collaboration with the Canadian Cancer Trials Group and funding from Celgene Corporation are conducting a new trial, the EORTC-1709-BTG, which is a Phase III trial of marizomib in combination with standard temozolomide-based radiochemotherapy versus standard temozolomide-based radiochemotherapy alone in patients with newly diagnosed glioblastoma. Marizomib is a natural marine product, which has been shown in pre-clinical studies to rapidly cross the blood-brain barrier (BBB) and stop pathways that target proteins in the brain. The trial will recruit 750 patients and is currently recruiting in 9 institutes in 6 countries. Read more.
First findings of All.Can patient survey presented at UK Parliament event
The All.Can initiative has presented findings of its UK patient survey at a UK Parliamentary event. They showed that 36% of people considered the cancer diagnosis stage as the biggest cause of inefficiency in their care. Two in five people with cancer had been initially misdiagnosed with something else – sometimes on multiple occasions – and one in five had to wait more than six months for a cancer diagnosis. All.Can is an international multi-stakeholder policy initiative that is focused on improving efficiency in cancer care, in which the IBTA is one of the stakeholder organisations. The UK national initiative is the first of nine countries to release findings from the All.Can patient survey. A report of the findings from all countries is due to be published in early 2019. Read more.
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From the brain tumour community
The EndBrainCancer Initiative launches two new programs to increase clinical trial enrolment of brain tumour patients
The EndBrainCancer Initiative (a US-based non-profit, formerly the Chris Elliott Fund) has announced the launch of two new initiatives, ‘First Step’ and ‘Team Up’, that are designed to accelerate research and promote clinical trial enrolment. The ‘First Step’ Initiative invites brain tumour patients to use an online form to indicate that they are interested in participating in genomic/biomarker testing and in clinical trials. The ‘Team Up’ initiative is an effort to invite local doctors and hospitals to indicate their interest in principle, via an online form, to increase the opportunity for their patients to have their tumour tissue saved, have their tumour tissue genomic/biomarker profiled, connect with specific specialists and neurosurgeons, and to participate in clinical trials. Read more.
Patient advocates travel to Washington DC to support ‘DIPG Awareness Resolution’
The DIPG Advocacy Group, a US-based association of individual advocates and foundations for children with diffuse intrinsic pontine glioma (DIPG), went to Washington DC this month in support of House Resolution 69, also known as the ‘DIPG Awareness Resolution’. The Resolution designates May 17 each year as ‘DIPG Awareness Day’; asks that paediatric and high-mortality rate cancers receive greater consideration in the research grant process; raises awareness about the devastating statistics for DIPG and paediatric brain cancer, and the need for greater paediatric cancer research in general. Read more.
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Research roundup
Results from phase 2 REGOMA trial of regorafenib vs lomustine in relapsed glioblastoma shows regorafenib survival benefit
A randomised, multicentre phase 2 trial performed across ten centres in Italy has demonstrated an “encouraging overall survival benefit” of the anticancer agent regorafenib in recurrent glioblastoma, according to results published in The Lancet Oncology. 119 glioblastoma patients who had surgery followed by radiotherapy in combination with temozolomide and then adjuvant temozolomide but who subsequently experienced progression were randomly assigned to receive regorafenib (n=59) or lomustine (n=60). Overall survival was 7·4 months in the regorafenib group and 5·6 months in the lomustine group. Regorafenib should be investigated in an adequately powered phase 3 trial, the study’s authors conclude. Read more (payment/subscription required for full paper).
Low‐grade glioma clinical conundrums: What distinguishes high-risk from low-risk?
Writing in the journal Cancer, Dr Marjolein Geurts and Prof Martin J. van den Bent discuss the clinical challenges of distinguishing high and low-risk patients who have a low-grade glioma diagnosis. They consider the unanswered questions and argue that with the arrival of a molecular classification, the clinical concept of ‘high risk’ needs rethinking because the presence of an IDH mutation is a more accurate prognostic marker than the classical criteria. Read more (full article available).
Animal and cell experiments suggest sorafenib and tumour-treating fields may be an effective combination therapy
Results of experiments published in the International Journal of Molecular Sciences have shown that the anticancer agent sorafenib appears to make glioblastoma cells more sensitive to tumour-treating fields (TTFields), suggesting a potential combination therapy. Animal and cell-based experiments demonstrated the combination was slightly better than each individual therapy and the paper’s authors conclude that these findings provide a molecular basis for the use of chemotherapeutic drugs as TTFields sensitizers to treat cancer. Read more (full paper available).
Comprehensive molecular analysis of neurofibromatosis type 1 gliomas offers new treatment avenues
Brain tumours arising in patients affected by neurofibromatosis type 1 (NF1) may be vulnerable to immunotherapy and targeted therapies, according to findings published in Nature Medicine. An international consortium of researchers performed an in-depth analysis of brain tumour samples from 56 patients to create a comprehensive inventory of the genetic, epigenetic, and immune alterations in NF1 gliomas. Among the findings include the discovery that approximately 50 percent of the slow-growing NF1 gliomas contained large numbers of T cells, making them good candidates for treatment with immunotherapy. Read more.
Updated Cochrane review: "no evidence" that anti-angiogenic therapy improves overall survival over chemotherapy in newly diagnosed glioblastoma
An updated systematic review by Cochrane of randomised clinical trials of anti-angiogenic therapy (e.g. bevacizumab/Avastin) in brain tumours has found that "while there is strong evidence that bevacizumab (an anti-angiogenic drug) prolongs progression-free survival in newly diagnosed and recurrent glioblastoma, the impact of this on quality of life and net clinical benefit for patients remains unclear". The review concluded that there is "no evidence of prolonging life over chemotherapy". The review authors add that "when anti-angiogenic therapies are used in combination with certain chemotherapy regimes there may be a small improvement in survival ... Not addressed here is whether subsets of people with glioblastoma may benefit from anti-angiogenic therapies". Read more.
The EORTC Brain Tumour Group and Protagen AG announce their collaboration to investigate the immuno-competence of long-term glioblastoma survivors
The European Organisation for Research and Treatment of Cancer (EORTC) Brain Tumour Group and Protagen AG have announced a collaboration that uses Protagen’s Cancer Immunotherapy Array to investigate the immunological profile and immuno-competence of long-term glioblastoma survivors to learn how to predict such long-term survival and potentially define novel pathways for therapeutic intervention. Read more (company press release).
Study reveals insights into glioblastoma-associated epilepsy
A paper published in Nature Communications has revealed that ‘perineuronal nets’, which are structures wrapped around neurons in the brain, play a role in tumour-associated epilepsy. They serve to modulate electrical impulses but are destroyed by enzymes produced by glioblastoma tumours. Blocking the digestion of perineuronal nets by these enzymes may provide therapeutic benefits, the study’s authors suggest. Read more.
Daily aspirin use linked to lower glioma risk, large epidemiological study finds
A study published in the journal Cancer Epidemiology, Biomarkers and Prevention has examined the association between glioma and aspirin or non-steroidal anti-inflammatory drug (NSAID) use. Using data from the Glioma International Case-Control Study (GICC), consisting of 4,533 glioma cases and 4,171 controls recruited between 2010-2013, alongside data from five previous studies, this meta-analysis found that aspirin may be associated with a reduced risk of glioma. A history of daily aspirin use for six months or longer was associated with a 38% lower glioma risk, compared to not having a history of daily aspirin use. Read more (payment/subscription required for full paper).
Study identifies specific gene 'silencing' microRNA molecules linked with paediatric brain tumours
Findings from experiments on brain tumour cells published in Scientific Reports support the idea that increasing levels of microRNAs may be a potential means of treating paediatric low-grade gliomas (PLGG). MicroRNA molecules are known to silence certain genes linked to PLGG development and growth. This study identified a subset of microRNAs (miR-125) that, in sufficient quantity, were effective in reducing tumour cell division and invasion, suggesting a potential new avenue for future therapies. Read more.
Next-generation sequencing technology can give full molecular brain tumour diagnosis with one test, research finds
A single assessment using next-generation DNA sequencing technology (NGS) is sufficient to accurately diagnose glioma in the majority of cases, according to a study published in Acta Neuropathologica Communications. The report evaluated a custom tailored NGS platform (used since 2013 at the Brain Tumor Center at Erasmus MC Cancer Institute, Rotterdam, The Netherlands) on 434 brain tumour samples. The technology allowed for the molecular assessments required for the WHO classification of diffuse gliomas, including the recent recommendations to assess copy number alterations of chromosomes 7 and 10, and of the TERT promoter region in IDH “wild type” lower grade gliomas Read more (full paper available).
Cognitive decline associated with brain tumour radiation therapy may be preventable with drug, study suggests
The first animal model of glioma that can also be used to study the long-term effects of radiation therapy has been developed, according to a study published in the journal eLife. Using this mouse model, researchers showed that a drug that temporarily suppresses a key component of the brain's immune system (a Colony-Stimulating Factor 1 inhibitor) can prevent radiation-associated cognitive decline. Read more.
Mutational landscape of secondary glioblastoma assessed and new targeted therapy trialled in clinical study
A study published in Cell has characterised the mutational landscape of secondary glioblastoma, the tumour type that some low-grade gliomas invariably progress to. Genetic analysis of 188 secondary glioblastoma tumours revealed that a significant proportion (approximately 14%) of patient tumour samples carried a new mutation, METex14 (some of those simultaneously harbour another mutation, named ZM fusion), which led to more aggressive tumour growth. A MET kinase inhibitor molecule named PLB-1001 that is able to penetrate the blood-brain barrier was identified and trialled as part of this research. PLB-1001 achieved partial response in at least two advanced secondary glioblastoma patients with “rarely significant side effects”, indicating a clinical potential for treating MET-altered gliomas using this therapy. Read more.
Pilot study for new cell-based model of meningioma published
A method for growing meningioma cells in the lab that is suitable for assessing the effects of radiation therapy has been described in an open-access paper published in the Journal of Neuroscience Methods. The paper’s authors explain in this pilot study that the scarcity of meningioma models represents the major obstacle to understanding the molecular basis of meningioma tumorigenesis. Read more (full paper available).
Researchers test nanoparticle-carrying neutrophils for targeted glioma therapy and enhanced MRI tumour visibility
A team of researchers has developed a cell-based ‘trojan horse’ for glioma therapy and imaging, which uses neutrophil immune cells containing chemotherapy-loaded magnetic nanoparticles that selectively target inflamed brain tumour cells after surgical resection of the primary tumour. Published in Nature Communications, animal experiments demonstrated that neutrophils engineered to contain mesoporous silica nanoparticles (MMSNs) enhanced the visibility of the tumour under MRI while also delivering a sustained release of a chemotherapeutic agent (in this case, the drug doxorubicin). Read more.
The Ivy Brain Tumor Center announces first evidence of clinically-relevant activity of ribociclib in glioblastoma
The Ivy Brain Tumor Center, a research institute based in Arizona, USA, has announced in a press release that a clinical study has found that the drug ribociclib, which was recently approved for breast cancer, penetrates into brain tumours and may be a useful part of treatment for glioblastoma. They report on an innovative phase 0/2 study that showed that even though ribociclib is able to get to the tumour region and stop tumour cells from dividing, some tumour cells are able to escape the treatment. Read more (press release).
Roswell Park Cancer Center reports that the immunotherapy SurVaxM appears to extend survival in newly diagnosed glioblastoma
Roswell Park Comprehensive Cancer Center has announced that the latest results from an ongoing phase 2 trial incorporating the immunotherapy SurVaxM, as part of combination treatment for newly diagnosed glioblastoma, show that the investigational drug is safe, well-tolerated and extended survival. According to a presentation at the Society for Neuro-Oncology (SNO) Annual Meeting in New Orleans, USA, 94.2% of the 63 study participants were alive one year after their diagnosis, as opposed to 65% of patients in a historical comparison group. Read more (press release).
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Company News
Bayer’s Regorafenib is the First Drug to Enter GBM AGILE study
The Global Coalition for Adaptive Research (GCAR) and Bayer have announced that Bayer’s regorafenib will be the first drug to enter “GBM AGILE” (Glioblastoma Adaptive Global Innovative Learning Environment), which is a revolutionary patient-centred adaptive platform trial that will evaluate multiple therapies for patients with newly diagnosed and recurrent glioblastoma. Read more (company press release).
US FDA approves larotrectinib (Vitrakvi) for patients with advanced solid tumours with an NTRK gene fusion
Bayer has announced that the US Food and Drug Administration (FDA) has approved larotrectinib (Vitrakvi), the first oral TRK inhibitor, for the treatment of adult and paediatric patients with solid tumours that harbour neurotrophic receptor tyrosine kinase (NTRK) gene fusion without a known acquired resistance mutation, are metastatic, or where surgical resection is likely to result in severe morbidity, and have no satisfactory alternative treatments or that have progressed following treatment. NTRK gene fusions occur across a broad range of tumour types in both adult and paediatric patients, including a small number of brain tumour patients with various gliomas. Read more (company press release).
Ziopharm Oncology presents Controlled IL-12 platform update and phase 1 trial data
Ziopharm Oncology gave an update on its Controlled IL-12 platform following a presentation of positive data from its phase 1 clinical trial in recurrent glioblastoma at the Society for Neuro-Oncology (SNO) annual meeting in New Orleans last month. Among their announcements, they stated that the median overall survival for Ad-RTS-hIL-12 plus veledimex in patients receiving low-dose steroids was 17.8 months. Read more (company press release).
Agios gives updated data from phase 1 trial of AG-881 in patients with IDH mutant positive advanced glioma
Agios presented updated data from an ongoing phase 1 study evaluating single agent AG-881 in advanced glioma at the Society for Neuro-Oncology (SNO) Annual Meeting in New Orleans in November, which provides evidence of prolonged disease control. AG-881 is an investigational, oral, selective, potent inhibitor of the mutant isocitrate dehydrogenase-1 (IDH1) and IDH2 enzymes and was designed for enhanced brain penetrance for development in IDH-mutant glioma. Read more (company press release).
Trial data for VAL-083 presented by DelMar Pharmaceuticals
DelMar Pharmaceuticals presented clinical updates on VAL-083 from ongoing first- and second-line trials in patients with MGMT-unmethylated glioblastoma at the 23rd Annual Meeting and Education Day of the Society for Neuro-Oncology (SNO) held from November 15-18, 2018 in New Orleans. “What has become amply clear is that in this aggressive tumour type, which can double in size every 6-8 weeks, VAL-083 when used for two or more cycles can stabilise the tumour and slow down its incessant growth," commented Saiid Zarrabian, President and Chief Executive Officer. Read more (company press release). Further details on the studies can be found here (on DelMar website).
First recurrent glioblastoma patient in clinical trial of DNX-2440 receives treatment, DNAtrix announces
DNAtrix has reported that the first recurrent glioblastoma patient has received treatment with DNX-2440 – an oncolytic virus expressing OX40 ligand – in a phase 1 trial that is evaluating the safety and efficacy of the therapy given to patients for whom surgery is not possible or planned. The experimental adenovirus is injected into the tumour site at the time of biopsy using a cannula especially designed for virus injection. Read more (company press release).
Tocagen and NRG Oncology to collaborate on a phase 2/3 trial of Toca 511 & Toca FC in newly diagnosed glioblastoma
Tocagen and NRG Oncology, a member of the National Cancer Institute's (NCI) National Clinical Trial Network (NCTN), have announced that the NCI Cancer Therapy and Evaluation Program (CTEP) Brain Malignancies Steering Committee has approved a concept to develop a clinical trial using the investigational therapeutic regimen Toca 511 (vocimagene amiretrorepvec) and Toca FC (flucytosine, extended-release) for the treatment of patients with newly diagnosed glioblastoma. The proposed NRG-BN006 trial is designed to assess the benefit of adding Toca 511 and Toca FC to chemotherapy and radiation compared to standard of care alone. Read more (company press release).
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And also...
Considering the therapeutic role of temozolomide in cancers of the central nervous system
An article published in the journal Oncology gives an up-to-date review of the role of the chemotherapy agent temozolomide in the management of patients with primary brain tumours, brain metastases, leptomeningeal carcinomatosis, and other selected central nervous system cancers. Temozolomide has held a central role in the treatment of glioma for nearly two decades and this article serves as a timely reminder of the data supporting the use of temozolomide for brain tumours, as well as its toxicities. Read the article online here.
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Upcoming events
Patient events and conferences 2019
Rare Disease Day
28 February 2019
Head To The Hill 2019
5-7 May 2019
Washington DC, USA
Scientific conferences 2019
January
Brain 2019: 16th Asia Pacific Multidisciplinary Meeting for Nervous System Diseases (BRAIN), 3rd Asian CNS Germ Cell Tumour Conference (CNSGCT), 9th Interim Meeting of the International Chinese Federation of Neurosurgical Sciences (ICFNS)
18-20 January 2019
Hong Kong
Queen Square Multidisciplinary Neuro-oncology Teaching Course: Gliomas/Teenage and Young Adult Tumours
31 January 2019
London, UK
March
American Association of Cancer Research (AACR) 110th Annual Meeting 2019
29 March - 3 April 2019
Atlanta, Georgia, USA
April
24th Annual Neuro-Tumor Club Meeting at AACR
1 April 2019
Atlanta, Georgia
11th Annual Conference of Indian Society of Neuro-Oncology (ISNO)
5 – 7 April 2019
Bhopal, India
Queen Square Multidisciplinary Neuro-oncology Teaching Course: Benign and Metastatic Tumours
11 April 2019
London, UK
May
SNO Pediatric Neuro-Oncology Basic and Translational Research Conference
3-4 May 2019
San Francisco, California, USA
5th EORTC Quality of Life and Cancer Clinical Trials Conference
16-17 May 2019
Brussels, Belgium
3rd Molecular Pathology Symposium 2019 | 2nd Asia Pacific Molecular Brain Tumour Course
18-19 May 2019
Gold Coast, Australia
Association of British Neurologists (ABN) Annual Meeting 2019
21-23 May 2019
Edinburgh, UK
Brain Tumor Meeting 2019
23-24 May 2019
Berlin, Germany
American Society of Clinical Oncology (ASCO) 2019 Annual Meeting
31 May-4 June 2019
Chicago, Illinois, USA
If you are organising or are aware of a forthcoming patient or brain tumour advocacy event or a scientific conference taking place in 2019 then please let us know by emailing chair@theibta.org so that we can also include it on our events page.
Keep up to date with future scientific conferences and events on the IBTA website conferences page here.
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The International Brain Tumour Alliance was established in 2005. It is a network of support, advocacy and information groups representing brain tumour patients and carers in different countries and also includes researchers, scientists, clinicians and allied health professionals who work in the field of brain tumours.
For more information, please visit www.theibta.org.
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We love to hear from you if you have any news that you would like to share with the IBTA community. Just send us an email: chair@theibta.org.
We will do our best to relay as much information as possible to our subscribers via this monthly newsletter and our website. The selection of e-News entries is at the sole discretion of the editors.
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