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e-Poster Display Session

1P - Real-world Frequency of Non-Small Cell Lung Cancer with Epidermal Growth Factor Receptor (EGFR) Exon 20 Insertion (Exon20ins) Mutations by Site of Insertion

Date

24 Mar 2021

Session

e-Poster Display Session

Presenters

Santiago Viteri

Citation

Journal of Thoracic Oncology (2021) 16 (suppl_4): S699-S703.

Authors

S. Viteri1, J.M. Bauml2, L. Bazhenova3, S.I. Ou4, N. Girard5, M. Schaffer6, J. Rose6, J. Curtin6, J. Karkera6, P. Mahadevia7, A.R. Minchom8

Author affiliations

  • 1 Dr Rosell Oncology Institute, Dexeus University Hospital, QuironSalud Group, Barcelona/ES
  • 2 Perelman School of Medicine at the University of Pennsylvania, 19104 - Philadelphia/US
  • 3 Moores Cancer Center - UC San Diego Health, La Jolla/US
  • 4 University of California Irvine, Orange/US
  • 5 Institut Curie, 75005 - Paris/FR
  • 6 Janssen R&D, Spring House/US
  • 7 Janssen Pharmaceuticals, 8869 - Raritan/US
  • 8 The Royal Marsden Hospital - NHS Foundation Trust, London/GB
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Abstract 1P

Background

EGFR Exon20ins mutations are in-frame insertions or duplications clustered around 3 key regions of Exon 20: helical (amino acid [AA] 762–766), near loop (767–772), and far loop (773–775). The site of insertion can influence the outcome to EGFR tyrosine kinase inhibitor therapy; loop insertions are typically resistant while some helical insertions are sensitive (Yasuda Lancet Oncol 13:23; Sci Transl Med 5:216ra177). We used real-world US genomic data from patients (pts) with lung adenocarcinoma (LUAD) to determine the frequency of EGFR Exon20ins mutations by site of insertion.

Methods

Pts with EGFR Exon20ins mutations identified from US institutions by next-generation sequencing were extracted from the AACR Project Genomics Evidence Neoplasia Information Exchange (GENIE), v.8.5 (Cancer Discov 2017;7:818), FoundationInsights, and Guardant databases.

Results

From GENIE, 175/9,673 pts (1.8%) with LUAD had EGFR Exon20ins mutations: 72.0% were located in the near loop, 28.0% in the far loop, and none in the helical region (Table). The most frequent sites of insertion were AAs 770 (36.0%), 773 (26.9%), and 769 (21.7%). From FoundationInsights, 627/36,465 pts (1.7%) with LUAD had EGFR Exon20ins mutations: 67.8% were located in the near loop, 26.6% in the far loop, and 5.4% in the helical region. The most frequent sites of insertion were AAs 770 (28.1%), 769 (23.4%), and 773 (22.8%). One Exon20ins mutation at AA 793 was also identified (Table). From Guardant, 414/31,617 pts (1.3%) with LUAD had EGFR Exon20ins mutations. 65.9% were located in the near loop, 26.6% in the far loop, and 7.5% in the helical region (Table). The most frequent sites of insertion were AAs 770 (28.0%), 769 (24.2%), and 773 (22.9%).

Table 1P:

Exon20ins mutations by site of insertion

Insertion region of Exon 20, n (%)GENIE (N = 175)FoundationInsights (N = 627)Guardant (N = 414)
Helical (AA 762–766)034 (5.4)31 (7.5)
763033 (5.3)31 (7.5)
76401 (0.2)0
Near Loop (AA 767–772)126 (72.0)425 (67.8)273 (65.9)
7671 (0.6)5 (0.8)2 (0.5)
768013 (2.1)2 (0.5)
76938 (21.7)147 (23.4)100 (24.2)
77063 (36.0)176 (28.1)116 (28.0)
77117 (9.7)66 (10.5)35 (8.5)
7727 (4.0)18 (2.9)18 (4.3)
Far Loop (AA 773–775)49 (28.0)167 (26.6)110 (26.6)
77347 (26.9)143 (22.8)95 (22.9)
7741 (0.6)17 (2.7)15 (3.6)
7751 (0.6)7 (1.1)0
Other Regions (AA 776–823)01 (0.2)0
79301 (0.2)0

Conclusions

Three real-world databases identified the near loop as the most frequent insertion region of Exon 20 (∼70%). Exon20ins mutations were found less frequently in the far loop (∼30%) and helical (0–7.5%) regions

Editorial acknowledgement

Medical writing support was provided by Tracy T. Cao, PhD of Janssen Global Services, LLC and funded by Janssen Global Services, LLC.

Legal entity responsible for the study

Janssen R&D.

Funding

Janssen R&D.

Disclosure

S. Viteri: Advisory/Consultancy: Roche, BMS, Janssen; Speaker Bureau/Expert testimony: Roche, BMS, AstraZeneca; Travel/Accommodation/Expenses: MSD. J.M. Bauml: Advisory/Consultancy: Clovis, BMS, AstraZeneca, Celgene, Boehringer Ingelheim, Janssen, Merck, Guardant Health, Genentech, Takeda, Ayala, Regeneron, Inivata, Novartis; Research grant/Funding (institution): Merck, Clovis, Carevive Systems, Novartis, Bayer, Janssen, AstraZeneca, Takeda. L. Bazhenova: Advisory/Consultancy: J&J, Daichi, BI, BMS, Merk, Novartis, Regeneron, Genentech; Research grant/Funding (institution): Beyondspring; Shareholder/Stockholder/Stock options: Epic Sciences. S-H.I. Ou: Speaker Bureau/Expert testimony: Roche/Genentech, Takeda/ARIAD, AstraZeneca, Merck, Pfizer; Advisory/Consultancy: Pfizer, AstraZeneca, Takeda/ARIAD, Roche/Genentech, AnHeart Therapeutics; Shareholder/Stockholder/Stock options: Turning Point Therapeutics, Elevation Oncology. N. Girard: Advisory/Consultancy: Bristol-Myers Squibb, Merck Sharp & Dohme, AstraZeneca, Pfizer, Amgen, Takeda, Boehringer Ingelheim, Roche; Research grant/Funding (institution): Bristol-Myers Squibb, Boehringer Ingelheim, Roche, Janssen. M. Schaffer: Shareholder/Stockholder/Stock options: Johnson & Johnson; Full/Part-time employment: Janssen. J. Rose: Shareholder/Stockholder/Stock options: Johnson and Johnson; Full/Part-time employment: Janssen Inc. J. Curtin: Shareholder/Stockholder/Stock options: Johnson & Johnson; Full/Part-time employment: Janssen. J. Karkera: Shareholder/Stockholder/Stock options: Johnson & Johnson; Full/Part-time employment: Janssen. P. Mahadevia: Shareholder/Stockholder/Stock options: Johnson & Johnson; Full/Part-time employment: Janssen. A.R. Minchom: Honoraria (self): Janssen Pharmaceutica, Meck Pharmaceuticals, Novartis Oncology, Faron Pharmaceuticals, Bayer Pharmaceuticals; Travel/Accommodation/Expenses: LOXO oncology, Amgen Pharmaceuticals.

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