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  • / Next-generation sequencing (NGS) for identifying actionable molecular alterations in patients with newly diagnosed and recurrent IDHwt-glioblastoma (GBM): A large mono-institutional experience.

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

Abstract Poster

Authors

Marta Padovan

Marta Padovan

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

Marta Padovan , Marta Maccari , Alberto Bosio , Salvatore Vizzaccaro , Ilaria Cestonaro , Martina Corrà , Mario Caccese , Giulia Cerretti , Matteo Fassan , Vittorina Zagonel , Giuseppe Lombardi

Organizations

Department of Oncology, Oncology 1, Veneto Institute of Oncology IOV-IRCCS, Padua, Italy, Department of Medicine (DIMED), Surgical Pathology & Cytopathology Unit, University of Padua, Padua, Italy

Research Funding

No funding received

Background: NGS panels allow the identification of alterations within hundreds of cancer-related genes and can guide a personalized strategy in glioma treatment. Methods: From Nov 2019 to Jan 2022 at Veneto Institute of Oncology, Padua, Italy, a large cohort of IDHwt-GBM tissues was analyzed by NGS (FoundationOneCDx). We identified all potential actionable molecular alterations at diagnosis and/or at recurrence. High tumor mutational burden (TMB) was defined as ≥10 mutations/megabase. Results: We 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. Incidence of actionable molecular alterations in newly diagnosed and relapsed GBM samples is described in the Table. The incidence of alteration of EGFR (ampl/mut), RB1, PIK3CA was statistically different between the two subgroups of 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. Conclusions: NGS 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.

Gene alteration
All cases (out of 419 cases)
%
At Diagnosis (out of 351 cases)
%
At Recurrent (out of 68 cases)
%
p
CDKN2A
240
57,3
195
55,6
45
66,2
0,1
CDKN2B
221
52,7
180
51,3
41
60,3
0,1
EGFR ampl
163
38,9
129
36,8
34
50,0
0,04
PTEN loss
113
27,0
99
28,2
14
20,6
0,2
EGFR mut
102
24,3
78
22,2
24
35,3
0,02
RB1
98
23,4
47
13,4
51
75,0
0,0001
NF1
76
18,1
64
18,2
12
17,6
0,9
PIK3CA
75
17,9
55
15,7
20
29,4
0,009
CDK4
64
15,3
58
16,5
6
8,8
0,1
MDM2
45
10,7
42
12,0
3
4,4
0,08
BRCA1-2
44
10,5
33
9,4
11
16,2
0,1
POLE
34
8,1
29
8,3
5
7,4
0,9
PDGFRA
33
7,9
29
8,3
4
5,9
0,6
FGFR1-3
28
6,7
22
6,3
6
8,8
0,4
MYC
27
6,4
22
6,3
5
7,4
0,7
JAK
24
5,7
18
5,1
6
8,8
0,2
ROS1
21
5,0
19
5,4
2
2,9
0,5
MET mut
10
2,4
8
2,3
2
2,9
0,6
MET ampl
9
2,1
7
2,0
2
2,9
0,6
BRAF V600E
9
2,1
6
1,7
3
4,4
0,1
NTRK1-3
0
0,0
0
0,0
0
0,0
NA
H-TMB
18
4,3
12
3,4
6
8,8
0,09

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Abstract Details

Meeting

2022 ASCO Annual Meeting

Session Type

Poster Session

Session Title

Developmental Therapeutics—Molecularly Targeted Agents and Tumor Biology

Track

Developmental Therapeutics—Molecularly Targeted Agents and Tumor Biology

Sub Track

Tissue-Based Biomarkers

Citation

J Clin Oncol 40, 2022 (suppl 16; abstr 3139)

DOI

10.1200/JCO.2022.40.16_suppl.3139

Abstract #

3139

Poster Bd #

131

Abstract Disclosures

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