Analysing the genomes of exceptional responders to Avastin treatment will lead to the identification of pre-selection biomarkers for use in patients diagnosed with GBM. It will enable us to better define clinically-relevant molecular phenotypes that can be built on to facilitate better patient selection for Avastin and other anti-VEGF targeted regimens.
Questions cloud the value of Avastin for recurrent GBM and are addressed in this application:
- Why is a benefit from Avastin seen only in some patients?
- How do we preselect these patients?
- What new pathways should be targeted to optimise response and prolong survival?
"I’m a strong believer in the fact that we cannot treat all patients the same, and especially with brain tumours – every single tumour that we see is completely different."
A/Prof Kerrie McDonald
Contrasting the genomes of extraordinary responders and non-responders will identify the underlying molecular biology associated with the minority of patients that respond well to treatment with Avastin; with months of remission from their tumour.
The response rates and survival data for the CABARET study has only recently been made available. Significant progression free and overall survival benefit was not achieved. However there was a distinct subgroup of patients of whom derived significant benefit from Avastin. The expense of Avastin is more justifiable if a subset of patients can be identified in whom there is greater benefit.
The team envisage the signature derived from Aim 1 and validated in Aims 2 and 3 will lead to a practice change in the way patients are selected for treatment with anti-angiogenic agents such as Avastin. Pre-selection using these biomarkers will ensure long, durable and positive responses leading to longer survival times. Their findings may be incorporated into the next generation of COGNO clinical trials, either for validation, as stratification factors, or in a clinical trial design with patient selection determined by molecular or genetic factors.
The development of a well-designed, adequately powered and relevant clinical trial is key to ensuring translation of positive results into clinical practice. Coupling a translational study with inter-laboratory collaborations will assure that maximal impact on cancer control and cancer care will be obtained. Ultimately, we hope that the results coming out of this study will lead to a prospective phase II trial incorporating an adaptive design, implementing the biomarkers found in this current study.
Team & Partners
This will be a collaborative project between numerous groups, in particular COGNO, AGOG and the Kinghorn Centre for Clinical Genomics. Key to this project are: medical oncologists and pathologists involved in the multidisciplinary medical management of glioblastoma, contributing to patient recruitment, generation of clinical questions, and maintaining a focus on the clinical relevance of research questions and dissemination and implementation of findings. Molecular biologists and biostatisticians/bioinformaticians will, ensure access to state-of-the-art technology for conduct and analysis of “omics” studies, and biostatistical expertise.
- PI: Dr Kathryn Field, Royal Melbourne Hospital
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