Case Report: Afatinib Treatment in a Patient With NSCLC Harboring a Rare EGFR Exon 20 Mutation
Unlike most other primary epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancer (NSCLC), exon 20 insertions, comprising approximately 4% to 10% of all EGFR mutations, are generally considered to be resistant to EGFR tyrosine kinase inhibitors (TKIs). However, EGFR exon 20 i...
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doaj-85042a3ff8b84b48ba1aec215e208ab72021-01-26T15:00:11ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2021-01-011010.3389/fonc.2020.593852593852Case Report: Afatinib Treatment in a Patient With NSCLC Harboring a Rare EGFR Exon 20 MutationSabine Zöchbauer-Müller0Sabine Zöchbauer-Müller1Bettina Kaserer2Helmut Prosch3Agnieszka Cseh4Flavio Solca5Markus Johann Bauer6Leonhard Müllauer7Leonhard Müllauer8Clinical Division of Oncology, Department of Medicine I, Medical University of Vienna, Vienna, AustriaComprehensive Cancer Center, Vienna, AustriaInstitute of Pathology, Medical University of Vienna, Vienna, AustriaDepartment of Biomedical Imaging and Image-Guided Therapy, Medical University of Vienna, Vienna, AustriaBoehringer Ingelheim International GmbH, Ingelheim, GermanyBoehringer Ingelheim RCV GmbH & Co. KG, Vienna, AustriaBoehringer Ingelheim RCV GmbH & Co. KG, Vienna, AustriaComprehensive Cancer Center, Vienna, AustriaInstitute of Pathology, Medical University of Vienna, Vienna, AustriaUnlike most other primary epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancer (NSCLC), exon 20 insertions, comprising approximately 4% to 10% of all EGFR mutations, are generally considered to be resistant to EGFR tyrosine kinase inhibitors (TKIs). However, EGFR exon 20 insertions are structurally and pharmacologically heterogeneous, with variability in their position and size having implications for response to different EGFR TKIs. The second-generation ErbB family blocker, afatinib, is approved for the first-line treatment of EGFR mutation-positive NSCLC and has been shown to have a broad inhibitory profile against common and uncommon EGFR mutations. Here, we describe a patient with bilateral multifocal lung adenocarcinoma harboring a very rare EGFR exon 20 insertion (c.2317_2319dup3; p.H773dup), who has been receiving treatment with afatinib for 4.5 years. To our knowledge, this is the first report describing long-term benefit for a patient treated with afatinib with this rare exon 20 insertion. We are aware of two further cases with this rare EGFR mutation. One patient, also reported here, has early-stage lung adenocarcinoma and has not yet received systemic therapy for NSCLC. The other patient received afatinib in the context of a global compassionate use program and had progressive disease. Our findings may be of clinical relevance for patients carrying tumors with this rare mutation as epidemiological evidence suggests that p.H773dup may function as a driver mutation in NSCLC. Together with previous preclinical and clinical evidence for the activity of afatinib against certain EGFR exon 20 insertions, these findings warrant further investigation.https://www.frontiersin.org/articles/10.3389/fonc.2020.593852/fullafatinibEGFR mutationexon 20 insertionH773duplong-term responseNSCLC |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Sabine Zöchbauer-Müller Sabine Zöchbauer-Müller Bettina Kaserer Helmut Prosch Agnieszka Cseh Flavio Solca Markus Johann Bauer Leonhard Müllauer Leonhard Müllauer |
spellingShingle |
Sabine Zöchbauer-Müller Sabine Zöchbauer-Müller Bettina Kaserer Helmut Prosch Agnieszka Cseh Flavio Solca Markus Johann Bauer Leonhard Müllauer Leonhard Müllauer Case Report: Afatinib Treatment in a Patient With NSCLC Harboring a Rare EGFR Exon 20 Mutation Frontiers in Oncology afatinib EGFR mutation exon 20 insertion H773dup long-term response NSCLC |
author_facet |
Sabine Zöchbauer-Müller Sabine Zöchbauer-Müller Bettina Kaserer Helmut Prosch Agnieszka Cseh Flavio Solca Markus Johann Bauer Leonhard Müllauer Leonhard Müllauer |
author_sort |
Sabine Zöchbauer-Müller |
title |
Case Report: Afatinib Treatment in a Patient With NSCLC Harboring a Rare EGFR Exon 20 Mutation |
title_short |
Case Report: Afatinib Treatment in a Patient With NSCLC Harboring a Rare EGFR Exon 20 Mutation |
title_full |
Case Report: Afatinib Treatment in a Patient With NSCLC Harboring a Rare EGFR Exon 20 Mutation |
title_fullStr |
Case Report: Afatinib Treatment in a Patient With NSCLC Harboring a Rare EGFR Exon 20 Mutation |
title_full_unstemmed |
Case Report: Afatinib Treatment in a Patient With NSCLC Harboring a Rare EGFR Exon 20 Mutation |
title_sort |
case report: afatinib treatment in a patient with nsclc harboring a rare egfr exon 20 mutation |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Oncology |
issn |
2234-943X |
publishDate |
2021-01-01 |
description |
Unlike most other primary epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancer (NSCLC), exon 20 insertions, comprising approximately 4% to 10% of all EGFR mutations, are generally considered to be resistant to EGFR tyrosine kinase inhibitors (TKIs). However, EGFR exon 20 insertions are structurally and pharmacologically heterogeneous, with variability in their position and size having implications for response to different EGFR TKIs. The second-generation ErbB family blocker, afatinib, is approved for the first-line treatment of EGFR mutation-positive NSCLC and has been shown to have a broad inhibitory profile against common and uncommon EGFR mutations. Here, we describe a patient with bilateral multifocal lung adenocarcinoma harboring a very rare EGFR exon 20 insertion (c.2317_2319dup3; p.H773dup), who has been receiving treatment with afatinib for 4.5 years. To our knowledge, this is the first report describing long-term benefit for a patient treated with afatinib with this rare exon 20 insertion. We are aware of two further cases with this rare EGFR mutation. One patient, also reported here, has early-stage lung adenocarcinoma and has not yet received systemic therapy for NSCLC. The other patient received afatinib in the context of a global compassionate use program and had progressive disease. Our findings may be of clinical relevance for patients carrying tumors with this rare mutation as epidemiological evidence suggests that p.H773dup may function as a driver mutation in NSCLC. Together with previous preclinical and clinical evidence for the activity of afatinib against certain EGFR exon 20 insertions, these findings warrant further investigation. |
topic |
afatinib EGFR mutation exon 20 insertion H773dup long-term response NSCLC |
url |
https://www.frontiersin.org/articles/10.3389/fonc.2020.593852/full |
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