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. 2021 Oct 13;13(20):5132.
doi: 10.3390/cancers13205132.

EGFR Exon 20 Insertion in Metastatic Non-Small-Cell Lung Cancer: Survival and Clinical Efficacy of EGFR Tyrosine-Kinase Inhibitor and Chemotherapy

Samy Chelabi  1 , Xavier Mignard  1 , Karen Leroy  2   3 , Isabelle Monnet  4 , Solenn Brosseau  5 , Nathalie Theou-Anton  6 , Marie-Ange Massiani  7 , Sylvie Friard  8 , Boris Duchemann  9 , Elizabeth Fabre  10   11 , Etienne Giroux-Leprieur  12   13 , Jacques Cadranel  14   15 , Marie Wislez  1   3
Affiliations

EGFR Exon 20 Insertion in Metastatic Non-Small-Cell Lung Cancer: Survival and Clinical Efficacy of EGFR Tyrosine-Kinase Inhibitor and Chemotherapy

Samy Chelabi et al. Cancers (Basel). .

Abstract

EGFR exon 20 insertions are rare genetic alterations in non-small-cell lung cancers (NSCLCs) that are usually unresponsive to approved EGFR tyrosine kinase inhibitors (TKIs). In this paper, we describe the clinical characteristics, efficacy of EFGR TKIs and chemotherapy, and resulting survival in this population. We retrospectively collected patients with EGFR exon 20 insertions (Exon20ins) from 11 French genetic platforms and paired them (1:2 ratio) with classic Exon 19/21 EGFR mutation patients (controls). Between 2012 and 2017, 35 Exon20ins patients were included. These patients were younger at diagnosis than the controls. All Exon20ins patients who were treated with first-line EGFR TKIs (n = 6) showed progressive disease as the best tumor response. There was no significant difference in the tumor response or the disease control rate with first-line platinum-based chemotherapy between the two groups. A trend towards shorter overall survival was observed in Exon20ins vs. controls (17 months (14-not reach(NR) 95% confidence interval(CI) vs. 29 months (17-NR 95%CI), p = 0.09), respectively. A significant heterogeneity in amino acid insertion in EGFR exon 20 was observed. EGFR exon 20 insertions are heterogeneous molecular alterations in NSCLC that are resistant to classic EGFR TKIs, which contraindicates their use as a first-line treatment.

Keywords: EGFR; NSCLC; TKI; chemotherapy; exon 20 insertion; survival.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Comparative prevalence of EGFR exon 20 insertions in NSCLC between the CBio Cancer Genomics Portal database and the present study. Detailed insertions from amino acid positions 767 to 773 in EGFR exon 20: in blue, exon 20 insertions from CBio Cancer Genomics Portal, n(%); in red, detailed exon 20 insertions from our study, n(%).
Figure 2
Figure 2
Kaplan–Meier estimation of overall survival (OS) measured from the inclusion of patients in the Exon20ins and control groups.
Figure 3
Figure 3
Kaplan–Meier estimation of progression-free survival (PFS) measured from inclusion in patients with exon 20 insertion (A) and control patients (B). PFS was determined for all patients (red), first-line TKIs patients (blue), and first-line chemotherapy patients (green) in each group.
See this image and copyright information in PMC

References

    1. Barlesi F., Mazières J., Merlio J.-P., Debieuvre D., Mosser J., Léna H., Ouafik L., Besse B., Rouquette I., Westeel V., et al. Routine Molecular Profiling of Cancer: Results of a One-Year Nationwide Program of the French Cooperative Thoracic Intergroup (IFCT) for Advanced Non-Small Cell Lung Cancer (NSCLC) Patients. Lancet. 2016;287:1415–1426. doi: 10.1016/S0140-6736(16)00004-0. - DOI - PubMed
    1. Riess J., Gandare D., Frampton J., Madison R., Peled N., Bufill J., Dy G., Ou S., Stephens P., McPherson J., et al. Diverse EGFR Exon 20 Insertions and Co-Occurring Molecular Alterations Identified by Comprehensive Genomic Profiling of NSCLC. J. Thorac. Oncol. 2018;13:1560–1568. doi: 10.1016/j.jtho.2018.06.019. - DOI - PMC - PubMed
    1. Vyse S., Huang P.H. Targeting EGFR Exon 20 Insertion Mutations in Non-Small Cell Lung Cancer. Signal Transduct. Target. Ther. 2019;4:51. doi: 10.1038/s41392-019-0038-9. - DOI - PMC - PubMed
    1. Cerami E., Gao J., Dogrusoz U., Gross B.E., Sumer S.O., Aksoy B.A., Jacobsen A., Byrne C.J., Heuer M.L., Larsson E., et al. The CBio Cancer Genomics Portal: An Open Platform for Exploring Multidimensional Cancer Genomics Data. Cancer Discov. 2012;2:401–404. doi: 10.1158/2159-8290.CD-12-0095. - DOI - PMC - PubMed
    1. Gao J., Aksoy B.A., Dogrusoz U., Dresdner G., Gross B., Sumer S.O., Sun Y., Jacobsen A., Sinha R., Larsson E., et al. Integrative Analysis of Complex Cancer Genomics and Clinical Profiles Using the CBioPortal. Sci. Signal. 2013;6:pl1. doi: 10.1126/scisignal.2004088. - DOI - PMC - PubMed