L718Q/V mutation in exon 18 of EGFR mediates resistance to osimertinib: clinical features and treatment
Abstract Osimertinib, a mutant-specific third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), is emerging as the preferred first-line of treatment for EGFR-mutant lung cancer. However, osimertinib resistance inevitably develops among patients treated with the drug...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Springer
2022-08-01
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| Series: | Discover Oncology |
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| Online Access: | https://doi.org/10.1007/s12672-022-00537-7 |
| _version_ | 1811215894987145216 |
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| author | Meihui Li Jing Qin Fajun Xie Lei Gong Na Han Hongyang Lu |
| author_facet | Meihui Li Jing Qin Fajun Xie Lei Gong Na Han Hongyang Lu |
| author_sort | Meihui Li |
| collection | DOAJ |
| description | Abstract Osimertinib, a mutant-specific third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), is emerging as the preferred first-line of treatment for EGFR-mutant lung cancer. However, osimertinib resistance inevitably develops among patients treated with the drug. The modal resistance mechanisms of osimertinib include the occurrence of epithelial transition factor (c-MET) amplification and C797S mutation, whereas rare mutations are presented as case reports. Recently, the L718Q/V mutation in exon 18 of EGFR has been reported to contribute to one of the possible mechanisms of resistance. The clinical features and subsequent treatment strategies for this mutation require further research. This study retrospectively enrolled NSCLC patients with the L718Q/V mutation from 2017 to 2021 at the Cancer Hospital of the University of the Chinese Academy of Sciences (Zhejiang Cancer Hospital), as well as additional patients with the same mutation from PubMed literature, to summarize the clinical features of the mutation. The association between the detection of L718Q/V and resistance to osimertinib, as well as impacts on the therapeutic process and outcome, was analyzed. We included a total of two patients diagnosed at Zhejiang Cancer Hospital and twelve patients from the literature. Of the fourteen total patients, 64.3% were male and 35.7% were female. The average age of the group was 60.2 years (range 45–72). A history of tobacco use was common among the group. In all of the cases we considered, the L718Q/V mutation was secondary to the L858R mutation. The second-generation TKI afatinib was found to provide a high disease control rate (DCR) (85.7%, 6/7) and relatively low objective response rate (ORR) (42/9%, 3/7). The median progression free survival (mPFS) for this treatment reached 2 months (1–6 months). The patients failed to benefit from chemotherapy combined with immunotherapy or other TKI medications. Due to the limited number of cases considered in this study, future studies should explore drugs that more precisely target the L718Q/V mutation of EGFR exon 18. |
| first_indexed | 2024-04-12T06:30:01Z |
| format | Article |
| id | doaj.art-2c7398dc2b51465e9ac4c1f763e61f87 |
| institution | Directory Open Access Journal |
| issn | 2730-6011 |
| language | English |
| last_indexed | 2024-04-12T06:30:01Z |
| publishDate | 2022-08-01 |
| publisher | Springer |
| record_format | Article |
| series | Discover Oncology |
| spelling | doaj.art-2c7398dc2b51465e9ac4c1f763e61f872022-12-22T03:44:02ZengSpringerDiscover Oncology2730-60112022-08-011311810.1007/s12672-022-00537-7L718Q/V mutation in exon 18 of EGFR mediates resistance to osimertinib: clinical features and treatmentMeihui Li0Jing Qin1Fajun Xie2Lei Gong3Na Han4Hongyang Lu5Zhejiang Key Laboratory of Diagnosis & Treatment Technology On Thoracic Oncology (Lung and Esophagus), Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital)Zhejiang Key Laboratory of Diagnosis & Treatment Technology On Thoracic Oncology (Lung and Esophagus), Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital)Zhejiang Key Laboratory of Diagnosis & Treatment Technology On Thoracic Oncology (Lung and Esophagus), Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital)Zhejiang Key Laboratory of Diagnosis & Treatment Technology On Thoracic Oncology (Lung and Esophagus), Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital)Zhejiang Key Laboratory of Diagnosis & Treatment Technology On Thoracic Oncology (Lung and Esophagus), Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital)Zhejiang Key Laboratory of Diagnosis & Treatment Technology On Thoracic Oncology (Lung and Esophagus), Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital)Abstract Osimertinib, a mutant-specific third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), is emerging as the preferred first-line of treatment for EGFR-mutant lung cancer. However, osimertinib resistance inevitably develops among patients treated with the drug. The modal resistance mechanisms of osimertinib include the occurrence of epithelial transition factor (c-MET) amplification and C797S mutation, whereas rare mutations are presented as case reports. Recently, the L718Q/V mutation in exon 18 of EGFR has been reported to contribute to one of the possible mechanisms of resistance. The clinical features and subsequent treatment strategies for this mutation require further research. This study retrospectively enrolled NSCLC patients with the L718Q/V mutation from 2017 to 2021 at the Cancer Hospital of the University of the Chinese Academy of Sciences (Zhejiang Cancer Hospital), as well as additional patients with the same mutation from PubMed literature, to summarize the clinical features of the mutation. The association between the detection of L718Q/V and resistance to osimertinib, as well as impacts on the therapeutic process and outcome, was analyzed. We included a total of two patients diagnosed at Zhejiang Cancer Hospital and twelve patients from the literature. Of the fourteen total patients, 64.3% were male and 35.7% were female. The average age of the group was 60.2 years (range 45–72). A history of tobacco use was common among the group. In all of the cases we considered, the L718Q/V mutation was secondary to the L858R mutation. The second-generation TKI afatinib was found to provide a high disease control rate (DCR) (85.7%, 6/7) and relatively low objective response rate (ORR) (42/9%, 3/7). The median progression free survival (mPFS) for this treatment reached 2 months (1–6 months). The patients failed to benefit from chemotherapy combined with immunotherapy or other TKI medications. Due to the limited number of cases considered in this study, future studies should explore drugs that more precisely target the L718Q/V mutation of EGFR exon 18.https://doi.org/10.1007/s12672-022-00537-7L718Q/V mutation of EGFR exon 18EGFR T790M mutationOsimertinibResistance mechanismAfatinib |
| spellingShingle | Meihui Li Jing Qin Fajun Xie Lei Gong Na Han Hongyang Lu L718Q/V mutation in exon 18 of EGFR mediates resistance to osimertinib: clinical features and treatment Discover Oncology L718Q/V mutation of EGFR exon 18 EGFR T790M mutation Osimertinib Resistance mechanism Afatinib |
| title | L718Q/V mutation in exon 18 of EGFR mediates resistance to osimertinib: clinical features and treatment |
| title_full | L718Q/V mutation in exon 18 of EGFR mediates resistance to osimertinib: clinical features and treatment |
| title_fullStr | L718Q/V mutation in exon 18 of EGFR mediates resistance to osimertinib: clinical features and treatment |
| title_full_unstemmed | L718Q/V mutation in exon 18 of EGFR mediates resistance to osimertinib: clinical features and treatment |
| title_short | L718Q/V mutation in exon 18 of EGFR mediates resistance to osimertinib: clinical features and treatment |
| title_sort | l718q v mutation in exon 18 of egfr mediates resistance to osimertinib clinical features and treatment |
| topic | L718Q/V mutation of EGFR exon 18 EGFR T790M mutation Osimertinib Resistance mechanism Afatinib |
| url | https://doi.org/10.1007/s12672-022-00537-7 |
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