Dataset Information

Intellance-2: omics data on recurrent glioblastoma patients participating in the Intellance-2 clinical trial, prior to treatment.

ABSTRACT: This study contains omics data from patients from the Intellance-2 clinical trial, in which effectiveness of ABT414 in EGFR amplified recurrent glioblastoma patients was tested. Patients were randomly assigned to one of three arms: (1) standard of care treatement (TMZ or CCNU), (2) Only ABT414 and (3) ABT414 + (TMZ|CCNU)

PROVIDER: EGAS00001005437 | EGA |

REPOSITORIES: EGA

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Publications

EGFR mutations are associated with response to depatux-m in combination with temozolomide and result in a receptor that is hypersensitive to ligand.

Hoogstrate Youri Y Vallentgoed Wies W Kros Johan M JM de Heer Iris I de Wit Maurice M Eoli Marica M Sepulveda Juan Manuel JM Walenkamp Annemiek M E AME Frenel Jean-Sebastien JS Franceschi Enrico E Clement Paul M PM Weller Micheal M van Royen Martin E ME Ansell Peter P Looman Jim J Bain Earle E Morfouace Marie M Gorlia Thierry T Golfinopoulos Vassilis V van den Bent Martin M French Pim J PJ

Neuro-oncology advances 20191209 1

<h4>Background</h4>The randomized phase II INTELLANCE-2/EORTC_1410 trial on EGFR-amplified recurrent glioblastomas showed a trend towards improved overall survival when patients were treated with depatux-m plus temozolomide compared with the control arm of alkylating chemotherapy only. We here performed translational research on material derived from this clinical trial to identify patients that benefit from this treatment.<h4>Methods</h4>Targeted DNA-sequencing and whole transcriptome analysis ...[more]

PMID: 32642719

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Project description:Introduction: The EORTC22033-26033 clinical trial investigated whether initial temozolomide (TMZ) chemotherapy confers survival advantage compared to radiotherapy (RT) in low grade glioma patients. In this study we performed gene expression profiling on tissues from this trial in order to identify markers associated with progression free survival and treatment response in this well-defined cohort of patients. Methods: Gene expression profiling, performed on 195 samples, was used to assign tumors to one of six intrinsic glioma subtypes (IGS; molecularly similar tumors predefined by unsupervised gene expression analysis) and to extract the cellular composition of immune infiltrates. DNA copy number changes were determined on samples assigned to IGS-16. Results: We confirm that IGS-subtypes are prognostic in EORTC22033-26033 clinical trial samples. Specific genetic changes segregate in distinct IGS subtypes: most samples assigned to IGS-9 have IDH-mutations combined with 1p19q codeletion, samples assigned to IGS-17 have IDH-mutations with intact 1p19q chromosomal arms and samples assigned to other intrinsic subtypes often are IDH-wildtype and 1p19q intact. A trend towards benefit from RT compared to TMZ was observed for samples assigned to IGS-9 (HR for TMZ is 1.90, 95% CI [0.95, 3.80], P=0.065), but not for samples assigned to IGS-17 (HR for TMZ vs RT is 0.87, 95% CI[0.50, 1.51], P=0.62). We did not identify genes significantly associated with progression free survival (PFS) within intrinsic subtypes, though follow-up time is limited. We also show that LGGs and GBMs differ in their immune-infiltrate with LGGs having higher suppressor and lower effector cell populations compared to GBMs. This suggests that LGGs are less amenable to checkpoint inhibitor type immune therapies than GBMs. Gene expression analysis and copy number analysis also identified one patient with a pilocytic astrocytoma (PA). Conclusion: Intrinsic glioma subtypes are prognostic for PFS in EORTC22033-26033 clinical trial samples.

Dataset Information

Intellance-2: omics data on recurrent glioblastoma patients participating in the Intellance-2 clinical trial, prior to treatment.

Publications

EGFR mutations are associated with response to depatux-m in combination with temozolomide and result in a receptor that is hypersensitive to ligand.

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