Study Explores Tumor Genotyping in Patients Newly Diagnosed with Glioblastoma

Prospective genomics can inform subsequent clinical trial analysis aiming at matching outcome with tumor genotyping.

Glioblastoma (GB) is an aggressive type of central nervous system tumor that forms on the supportive tissue of the brain. Researchers posit that it may be improved by multi-dimensional genomic analyses. However, such analyses are not widely available as routine clinical care.

At the 2018 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, investigators discussed ALLELE, an ABC2-funded consortium to produce prospective clinical genomics in addition to developing novel biomarkers to be used in GB patients.

In a multi-center prospective study of tumor genotyping in recently diagnosed GB, investigators sought to assess the practicality of genotyping tumors in a time-frame to support real-time use in clinical trials.

For their study, chromosomal microarray (CMA) and clinical (CLIA) genome-wide tumor whole exome sequencing (WES) were completed, following surgery. In order to inform best practices, the investigators included comparisons with orthogonal genomic and functional methods.

As of January 30, 2018, a total of 46 patients with GB were enrolled, spanning 5 study sites; the median age of the participants enrolled was 60.

In 39 patients, WES and CMA were completed with a median time of 51 days between surgery and biomarker analysis completion. Activating BRAF and FGFR1 mutations were discovered in 2 patients, and, based on genomics, 2 tumors were redefined.

Additionally, the authors add that 26 patients with MGMT unmethylated GB were enrolled in a companion randomized multi-arm trial, dubbed INSIGhT, comparing the standard of care with adjuvant CC-115, neratinib, or abemaciclib in newly diagnosed GB (NCT02977780). In the future, investigators will assess pre-defined biomarker groups—EGFR-, PI3K- and CDK-positive—for “their ability to predict outcome in each arm,” authors of the abstract write.

Ten patients were administered the standard of care, and 3 patients participated in other clinical trials. Exploratory functional biomarker assays were also generated on live cells from freshly resected tumors, and patient-derived GB cell line models were obtained in a subset of patients.

Based off of the study’s results, it was concluded that, within a clinically acceptable time frame following surgery for patients with newly diagnosed GB, molecular profiling with WES and CMA is possible. It was also noted that, when conducted in a prospective manner, genomic analyses have the capability to inform subsequent clinical trial analyses that aim at pairing outcomes with tumor genotyping.

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