BIOM-19 - Next-generation sequencing (NGS) for identifying actionable molecular alterations in newly diagnosed and recurrent IDHwt-glioblastoma (GBM) patients: a large mono institutional experience

Friday, November 18, 2022

7:30 PM – 9:30 PM ET

Location: West/Central Hall

Poster Presenter(s)

Andrea Pace, Chief

IRCCS Regina Elena Cancer Institute
Rome, Italy

Author(s)

MP

Marta Padovan, Medicine

Department of Oncology, Oncology 1, Veneto Institute of Oncology IOV-IRCCS, Padua, Italy
Padua, Italy
MM

Marta Maccari

Department of Oncology, Veneto Institute of Oncology IOV-IRCCS, Padua, Italy
Padua, Italy
AB

Alberto Bosio

Department of Oncology, Veneto Institute of Oncology IOV-IRCCS, Padua, Italy
Padua, Italy
SV

Salvatore Vizzaccaro

Department of Oncology, Oncology 1, Veneto Institute of Oncology IOV-IRCCS, Padua, Italy
Padua, Italy
IC

Ilaria Cestonaro

Department of Oncology, Oncology 1, Veneto Institute of Oncology IOV-IRCCS, Padua, Italy
Padua, Italy
MC

Martina Corrà

Department of Oncology, Oncology 1, Veneto Institute of Oncology IOV-IRCCS, Padua, Italy
Padua, Italy
Mario Caccese, Medicine

Department of Oncology, Oncology 1, Veneto Institute of Oncology IOV-IRCCS, Padua, Italy
Padua, Italy
GC

Giulia Cerretti, Medicine

Department of Oncology, Oncology 1, Veneto Institute of Oncology IOV-IRCCS, Padua, Italy
Padua, Italy
MF

Matteo Fassan

Department of Medicine (DIMED), Surgical Pathology Unit, University of Padua, Padua, Italy
Padua, Italy
VZ

Vittorina Zagonel, Medicine

Department of Oncology, Oncology 1, Veneto Institute of Oncology IOV-IRCCS, Padua, Italy
Padua, Italy

Author(s)

Giuseppe Lombardi, MD

Department of Oncology, Oncology 1, Veneto Institute of Oncology IOV-IRCCS, Padua, Italy
Padua, Italy

BACKGROUNDNGS panels allow the identification of alterations within hundreds of cancer-related genes and can guide a personalized strategy in glioma treatment. METHODSFrom Nov 2019 to Jan 2022 at Veneto Institute of Oncology, Padua, Italy, a large cohort of IDHwt-GBM tissues was analyzed by NGS (FoundationOne®CDx). We identified all potential actionable molecular alterations at diagnosis and/or at recurrence. High tumor mutational burden (TMB) was defined as ≥10 mutations/megabase. RESULTSWe analyzed 429 IDHwt-GBM samples: NGS profile was available for 419 samples (97.7%); sample failures in 10 cases (2.3%). 351 (84%) and 68 (16%) GBM samples derived from surgery at diagnosis and recurrence, respectively. All patients received radiotherapy and/or temozolomide as first line therapy. Among all the analyzed samples, the most frequent actionable molecular alterations were: CDKN2A (57%), CDKN2B (53%), EGFR amplification (39%), EGFR mutation (24%), PTEN loss (27%), RB1 (23%), NF1 (18%), PIK3CA (18%), CDK4 (15%), MDM2 (10%), PDGFRA (8%), BRCA1-2 (7%), FGFR1-3 (7%), Myc (6%), JAK (6%), ROS1 (5%), METmut (2%), METampl (2%), BRAF V600E (2%). No NTRK1/2/3 druggable alterations were observed. High TMB was found in 18 samples. The incidence of alteration of EGFR (ampl/mut), RB1, PIK3CA was statistically different between the two subgroups of newly diagnosed and recurrent GBM samples (Fisher test). To date, 10% of patients received a personalized treatment as compassionate use, off-label use or in clinical trials (9 Dabrafenib/Trametinib, 8 Alpelisib, 3 Erdafitinib, 2 Ipatasertib, 1 Alectinib, 1 Capmatinib, 1 Palbociclib, 1 Entrectinib, 1 Pamiparib). Activity analysis is still ongoing. CONCLUSIONNGS is feasible in GBM samples. Potentially, a high rate of patients could receive a personalized treatment. The activity analysis is ongoing. However, the incidence of actionable molecular alterations may differ between diagnosis and recurrent GBM samples.