81P - Implementing genomic profiling as standard-of-care for glioblastoma patients

Background

The introduction of molecular profiling and targeted therapies has only provided few new options for glioblastoma patients (pts). With a median survival of 16 months and no second-line standard therapy, new effective treatments are needed. Here, we report the results from Dept. of Oncology, Rigshospitalet, Denmark, where we investigated the impact of comprehensive molecular profiling in pts with glioblastoma, astrocytoma grade IV and diffuse midline glioma.

Methods

Eligible pts were ≥18 years of age, with newly diagnosed glioblastoma, astrocytoma grade IV or diffuse midline glioma between January 2020 and December 2021. Fresh tumor tissue was used for whole exome sequencing (WES) or whole genome sequencing (WGS) including germline analysis and somatic chromosomal aberrations analysis. Pts enrolled in 2020 had DNA analysed in the WES pipeline, and pts enrolled in 2021 in the WGS pipeline. Each genomic profile was presented at a weekly national molecular tumor board meeting for multidisciplinary evaluation, treatment recommendations and matching with clinical trials. Actionable targets have been classified according to the ESMO Scale for Clinical Actionability of molecular Targets (ESCAT).

Results

133 (92%) of the total 145 pts enrolled had tissue available for WES/WGS. As of now, for the 117 sequenced pts that have progressed after standard therapy, 8 patients (7%) have been treated with molecularly matched experimental therapies. 6 pts were treated in phase 1-2 clinical trials, 1 pt in compassionate use and 1 pt in a Named Patient Program. The actionable targets treated were TMB-high>10mut/MB (n=4), FGFR-mutations/-fusions (n=3) and a NTRK-fusion (n=1).

Conclusions

For glioblastoma, astrocytoma grade IV and diffuse midline glioma, genomic profiling revealed actionable targets and identified new therapeutic options. A full overview of actionable targets and clinical implications will be presented.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

M. Hoejgaard: Financial Interests, Personal, Other, Advisory Role for various diagnostic companies/investors: LingoMedical; Financial Interests, Personal, Stocks/Shares: Bavarian Nordic, Pacific Biosciences, Illumina Inc., Agilent; Financial Interests, Institutional, Funding: Roche; Non-Financial Interests, Personal, Principal Investigator: Repare Therapeutics, Amgen, Incyte Cooperation, Kinnate Biopharma; Other, Personal, Other, Board Member, Tumor Agnostic Board, Public service: Danish Medicines Council. I. Spanggaard: Financial Interests, Institutional, Invited Speaker: Roche, Puma Biotechnology, MSD, Genentech, Incyte, AstraZeneca, Orion, Pfizer; Non-Financial Interests, Personal, Principal Investigator: Roche, Puma Biotechnology, MSD, Genentech, Incyte, AstraZeneca, Orion, Pfizer. K.S. Rohrberg: Financial Interests, Personal, Invited Speaker: Bayer, Amgen, MSD; Financial Interests, Institutional, Invited Speaker, Compensation for conduction of clinical trial: Lilly, Roche/Genentech, Bristol-Myers Squibb, Symphogen, Pfizer, Novartis, Alligator Bioscience, Genmab, Bioinvent, Monta Bioscience; Financial Interests, Institutional, Other, Compensation for conduction of clinical trial: Bayer, Incyte, Puma Biotechnology, Orion Clinical. U.N. Lassen: Financial Interests, Personal, Advisory Board: Bayer, Novartis; Financial Interests, Institutional, Research Grant: Roche, BMS, Pfizer, GSK. All other authors have declared no conflicts of interest.