EGFR-Mutant Non-small Cell Lung Cancer: State-of-the-Art and Future Perspectives
EGFR mutations are the first identified targetable driver alterations in advanced non-small cell lung cancer (NSCLC), for which specific epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKI) have been developed. These small molecules, administered orally, changed the natural hist...
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European Medical Journal
2022-12-01
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| Series: | European Medical Journal |
| Online Access: | https://www.emjreviews.com/flagship-journal/article/egfr-mutant-non-small-cell-lung-cancer-state-of-the-art-and-future-perspectives/ |
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| author | Antonio Rossi Ettore Mari |
| author_facet | Antonio Rossi Ettore Mari |
| author_sort | Antonio Rossi |
| collection | DOAJ |
| description |
EGFR mutations are the first identified targetable driver alterations in advanced non-small cell lung cancer (NSCLC), for which specific epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKI) have been developed. These small molecules, administered orally, changed the natural history of patients with EGFR-mutated NSCLC, reporting impressive response and survival data. Osimertinib, a third-generation EGFR-TKI, can be considered the standard first-line therapy for the ‘common’ EGFR mutations, which include the exon 19 deletion and Leu858Arg point mutation in exon 21, accounting for 90% of cases. The ‘uncommon’ EGFR mutations, highly heterogeneous and with a low frequency, seem to be more sensitive to afatinib and osimertinib, a second-generation EGFR-TKI, excluding the EGFR exon 20 insertions mutations, for which a platinum-based regimen should be recommended while waiting for specific targeted inhibitors to reach the market. However, after an initial activity to first-line EGFR-TKI treatment, a disease progression is reported due to the presence of an intrinsic resistance or the onset of an acquired resistance. The latter can be broadly grouped into EGFR-dependent or EGFR-independent mechanisms of resistance, for which several new drugs and strategic approaches are under investigation. This review focuses on the state-of-the-art EGFR-TKIs in the treatment of metastatic NSCLC harbouring EGFR mutations, and also discusses potential future perspectives. |
| format | Article |
| id | doaj-art-52d1a037e56648a0babeffeb833a388f |
| institution | Kabale University |
| issn | 2397-6764 |
| language | English |
| publishDate | 2022-12-01 |
| publisher | European Medical Journal |
| record_format | Article |
| series | European Medical Journal |
| spelling | doaj-art-52d1a037e56648a0babeffeb833a388f2025-01-23T10:53:46ZengEuropean Medical JournalEuropean Medical Journal2397-67642022-12-0110.33590/emj/10136032EGFR-Mutant Non-small Cell Lung Cancer: State-of-the-Art and Future PerspectivesAntonio Rossi0Ettore MariOncology Centre of Excellence, Therapeutic Science & Strategy Unit, IQVIA, Milan, Italy EGFR mutations are the first identified targetable driver alterations in advanced non-small cell lung cancer (NSCLC), for which specific epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKI) have been developed. These small molecules, administered orally, changed the natural history of patients with EGFR-mutated NSCLC, reporting impressive response and survival data. Osimertinib, a third-generation EGFR-TKI, can be considered the standard first-line therapy for the ‘common’ EGFR mutations, which include the exon 19 deletion and Leu858Arg point mutation in exon 21, accounting for 90% of cases. The ‘uncommon’ EGFR mutations, highly heterogeneous and with a low frequency, seem to be more sensitive to afatinib and osimertinib, a second-generation EGFR-TKI, excluding the EGFR exon 20 insertions mutations, for which a platinum-based regimen should be recommended while waiting for specific targeted inhibitors to reach the market. However, after an initial activity to first-line EGFR-TKI treatment, a disease progression is reported due to the presence of an intrinsic resistance or the onset of an acquired resistance. The latter can be broadly grouped into EGFR-dependent or EGFR-independent mechanisms of resistance, for which several new drugs and strategic approaches are under investigation. This review focuses on the state-of-the-art EGFR-TKIs in the treatment of metastatic NSCLC harbouring EGFR mutations, and also discusses potential future perspectives.https://www.emjreviews.com/flagship-journal/article/egfr-mutant-non-small-cell-lung-cancer-state-of-the-art-and-future-perspectives/ |
| spellingShingle | Antonio Rossi Ettore Mari EGFR-Mutant Non-small Cell Lung Cancer: State-of-the-Art and Future Perspectives European Medical Journal |
| title | EGFR-Mutant Non-small Cell Lung Cancer: State-of-the-Art and Future Perspectives |
| title_full | EGFR-Mutant Non-small Cell Lung Cancer: State-of-the-Art and Future Perspectives |
| title_fullStr | EGFR-Mutant Non-small Cell Lung Cancer: State-of-the-Art and Future Perspectives |
| title_full_unstemmed | EGFR-Mutant Non-small Cell Lung Cancer: State-of-the-Art and Future Perspectives |
| title_short | EGFR-Mutant Non-small Cell Lung Cancer: State-of-the-Art and Future Perspectives |
| title_sort | egfr mutant non small cell lung cancer state of the art and future perspectives |
| url | https://www.emjreviews.com/flagship-journal/article/egfr-mutant-non-small-cell-lung-cancer-state-of-the-art-and-future-perspectives/ |
| work_keys_str_mv | AT antoniorossi egfrmutantnonsmallcelllungcancerstateoftheartandfutureperspectives AT ettoremari egfrmutantnonsmallcelllungcancerstateoftheartandfutureperspectives |