Concordance of Abundance for Mutational <i>EGFR</i> and Co-Mutational <i>TP53</i> with Efficacy of <i>EGFR</i>-TKI Treatment in Metastatic Patients with Non-Small-Cell Lung Cancer
The present study aimed to investigate the influence of the mutation abundance of the epidermal growth factor receptor (<i>EGFR</i>) and its co-mutation with <i>TP53</i> on the therapeutic efficacy of tyrosine kinase inhibitor (TKI) treatment in patients with metastatic lung...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-09-01
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| Series: | Current Oncology |
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| Online Access: | https://www.mdpi.com/1718-7729/30/9/616 |
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| author | Youping Wang Hong Liu Ningjuan Yu Xueping Xiang |
| author_facet | Youping Wang Hong Liu Ningjuan Yu Xueping Xiang |
| author_sort | Youping Wang |
| collection | DOAJ |
| description | The present study aimed to investigate the influence of the mutation abundance of the epidermal growth factor receptor (<i>EGFR</i>) and its co-mutation with <i>TP53</i> on the therapeutic efficacy of tyrosine kinase inhibitor (TKI) treatment in patients with metastatic lung adenocarcinoma (LUAD). In total, 130 patients (January 2018-September 2022) with metastatic LUAD from the Second Affiliated Hospital of Zhejiang University were included. Kaplan–Meier analysis was performed to measure the duration of drug application (DDA) and the log-rank test was used to compare differences. Univariate and multivariate analyses of Cox proportional hazard regression models were used to evaluate the association between the relevant clinicopathological factors and DDA. Hazard ratios with 95% confidence intervals were also calculated. Among the 130 patients who were treated with first-generation <i>EGFR</i>-TKIs, 86 showed high-<i>EGFR</i> mutation abundance (>22.0%) and 44 showed low-<i>EGFR</i> mutation abundance (≤22.0%). Patients in the high-<i>EGFR</i> group had a greater DDA than those in the low-<i>EGFR</i> group (<i>p</i> < 0.05). The results of the subgroup analysis were consistent with those of the total mutation population (exon19: >18.5% vs. ≤18.5%, 14 months vs. 10 months, <i>p</i> = 0.049; exon21: >22.0% vs. ≤22.0%, 15 months vs. 9 months, <i>p</i> = 0.005). In addition, the mutation abundance of <i>TP53</i> was negatively correlated with the DDA (<i>p</i> < 0.05). Patients in the combination group had a better DDA than those in the monotherapy group (<i>p</i> < 0.05). Subgroup analysis showed that, among the low mutation abundance of the <i>EGFR</i> exon 21 or 19 cohort, the combination group had a better DDA than the monotherapy group (<i>p</i> < 0.05). An <i>EGFR</i> mutation abundance greater than 22.0% was a positive predictor of DDA in patients with metastatic LUAD. However, a <i>TP53</i> mutation abundance higher than 32.5% could reverse this situation. Finally, first-line treatment with <i>EGFR</i>-TKIs plus chemotherapy is a potential treatment strategy for patients with low-abundance <i>EGFR</i> mutations. |
| first_indexed | 2024-03-10T22:53:41Z |
| format | Article |
| id | doaj.art-db3595b8ff4447caa0ac22b9b2369ae6 |
| institution | Directory Open Access Journal |
| issn | 1198-0052 1718-7729 |
| language | English |
| last_indexed | 2024-03-10T22:53:41Z |
| publishDate | 2023-09-01 |
| publisher | MDPI AG |
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| series | Current Oncology |
| spelling | doaj.art-db3595b8ff4447caa0ac22b9b2369ae62023-11-19T10:11:18ZengMDPI AGCurrent Oncology1198-00521718-77292023-09-013098464847610.3390/curroncol30090616Concordance of Abundance for Mutational <i>EGFR</i> and Co-Mutational <i>TP53</i> with Efficacy of <i>EGFR</i>-TKI Treatment in Metastatic Patients with Non-Small-Cell Lung CancerYouping Wang0Hong Liu1Ningjuan Yu2Xueping Xiang3Department of Medical Oncology, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, ChinaState Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou 510060, ChinaDepartment of Medical Oncology, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, ChinaDepartment of Pathology, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, ChinaThe present study aimed to investigate the influence of the mutation abundance of the epidermal growth factor receptor (<i>EGFR</i>) and its co-mutation with <i>TP53</i> on the therapeutic efficacy of tyrosine kinase inhibitor (TKI) treatment in patients with metastatic lung adenocarcinoma (LUAD). In total, 130 patients (January 2018-September 2022) with metastatic LUAD from the Second Affiliated Hospital of Zhejiang University were included. Kaplan–Meier analysis was performed to measure the duration of drug application (DDA) and the log-rank test was used to compare differences. Univariate and multivariate analyses of Cox proportional hazard regression models were used to evaluate the association between the relevant clinicopathological factors and DDA. Hazard ratios with 95% confidence intervals were also calculated. Among the 130 patients who were treated with first-generation <i>EGFR</i>-TKIs, 86 showed high-<i>EGFR</i> mutation abundance (>22.0%) and 44 showed low-<i>EGFR</i> mutation abundance (≤22.0%). Patients in the high-<i>EGFR</i> group had a greater DDA than those in the low-<i>EGFR</i> group (<i>p</i> < 0.05). The results of the subgroup analysis were consistent with those of the total mutation population (exon19: >18.5% vs. ≤18.5%, 14 months vs. 10 months, <i>p</i> = 0.049; exon21: >22.0% vs. ≤22.0%, 15 months vs. 9 months, <i>p</i> = 0.005). In addition, the mutation abundance of <i>TP53</i> was negatively correlated with the DDA (<i>p</i> < 0.05). Patients in the combination group had a better DDA than those in the monotherapy group (<i>p</i> < 0.05). Subgroup analysis showed that, among the low mutation abundance of the <i>EGFR</i> exon 21 or 19 cohort, the combination group had a better DDA than the monotherapy group (<i>p</i> < 0.05). An <i>EGFR</i> mutation abundance greater than 22.0% was a positive predictor of DDA in patients with metastatic LUAD. However, a <i>TP53</i> mutation abundance higher than 32.5% could reverse this situation. Finally, first-line treatment with <i>EGFR</i>-TKIs plus chemotherapy is a potential treatment strategy for patients with low-abundance <i>EGFR</i> mutations.https://www.mdpi.com/1718-7729/30/9/616non-small-cell lung adenocarcinoma<i>EGFR</i> mutation abundance<i>EGFR</i>-TKIs<i>TP53</i> co-mutation |
| spellingShingle | Youping Wang Hong Liu Ningjuan Yu Xueping Xiang Concordance of Abundance for Mutational <i>EGFR</i> and Co-Mutational <i>TP53</i> with Efficacy of <i>EGFR</i>-TKI Treatment in Metastatic Patients with Non-Small-Cell Lung Cancer Current Oncology non-small-cell lung adenocarcinoma <i>EGFR</i> mutation abundance <i>EGFR</i>-TKIs <i>TP53</i> co-mutation |
| title | Concordance of Abundance for Mutational <i>EGFR</i> and Co-Mutational <i>TP53</i> with Efficacy of <i>EGFR</i>-TKI Treatment in Metastatic Patients with Non-Small-Cell Lung Cancer |
| title_full | Concordance of Abundance for Mutational <i>EGFR</i> and Co-Mutational <i>TP53</i> with Efficacy of <i>EGFR</i>-TKI Treatment in Metastatic Patients with Non-Small-Cell Lung Cancer |
| title_fullStr | Concordance of Abundance for Mutational <i>EGFR</i> and Co-Mutational <i>TP53</i> with Efficacy of <i>EGFR</i>-TKI Treatment in Metastatic Patients with Non-Small-Cell Lung Cancer |
| title_full_unstemmed | Concordance of Abundance for Mutational <i>EGFR</i> and Co-Mutational <i>TP53</i> with Efficacy of <i>EGFR</i>-TKI Treatment in Metastatic Patients with Non-Small-Cell Lung Cancer |
| title_short | Concordance of Abundance for Mutational <i>EGFR</i> and Co-Mutational <i>TP53</i> with Efficacy of <i>EGFR</i>-TKI Treatment in Metastatic Patients with Non-Small-Cell Lung Cancer |
| title_sort | concordance of abundance for mutational i egfr i and co mutational i tp53 i with efficacy of i egfr i tki treatment in metastatic patients with non small cell lung cancer |
| topic | non-small-cell lung adenocarcinoma <i>EGFR</i> mutation abundance <i>EGFR</i>-TKIs <i>TP53</i> co-mutation |
| url | https://www.mdpi.com/1718-7729/30/9/616 |
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