478P - Molecular characterization of adult non-glioblastoma central nervous system (CNS) tumors to identify potential targettable alterations

Background

NGS panels in oncology offer personalized therapies based on genomic alterations, but data on their clinical use and efficacy for non-glioblastoma CNS tumors is limited.

Methods

This study aimed to explore the molecular landscape of non-glioblastoma CNS tumors in patients (pts) who underwent FoundationOne®CDx between 11/2019 and 04/2023 at Veneto Institute of Oncology, Padua (Italy), while also assessing access to TT. Analysis was conducted on archival tumor, comprising a cohort of 176 pts. Brain tumors were classified per WHO 2021.

Results

Our cohort was constituted by: 19 Grade 2 IDH mut astrocytomas (A); 35 G3 IDH mut A; 34 G4 A; 29 oligodendrogliomas; 4 diffuse midline gliomas; 3 gangliogliomas; 3 pleomorphic xanthoA; 30 meningiomas; 4 medulloblastomas; 5 ependymomas; 2 neuroblastomas; 3 schwannomas; 4 pituitary adenomas; 1 hemangiopericytoma. The most frequent targettable molecular alterations (ESCAT ESMO Scale IIB-IIIB) were: PIK3CA/B mut (14.2%), NF1 and NF2 mut (10.2 and 13% respectively), BRCA 1-2 mut (8%), POLE mut (7.4%), high tumor mutational burden (TMB) (>10 mut/megabase) (6.8%), PDGFRA alterations (6.2%), BRAF non-V600E alterations (5.1%), RET and ROS1 mut (3.4 and 2.8% respectively), MDM2 amplification (2.3%), FGFR1-2-3 alterations and H3K28M (1.7%), MET amplification (1.7%), ALK rearrangements (1%). NTRK fusions and BRAF V600E have not been detected. 3/4 medulloblastomas pts exhibited a PTCH1 mutation. 4 pts received TT at recurrence, within clinical trials: one with grade 3 meningioma and ALK rearrangement treated with alectinib, one with PTCH1 mutant medulloblastoma treated with vismodegib, and two with high TMB treated with nivolumab/ipilumumab. Immune checkpoint inhib have shown remarkable activity in a meningioma patient, who is undergoing treatment for 12 months and has achieved a complete response according to RANO criteria, while another has had stable disease with alectinib for 7 months. In other cases TT did not demonstrate activity.

Conclusions

The incidence of targettable molecular alterations in adult CNS tumor pts was lower than in GBM. Nevertheless, in a few selected cases TT have the potential to increase treatment options at recurrence and improve outcomes.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Veneto Institute of Oncology IOV-IRCCS, Padua, Italy.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.