A Large Real-World Study on the Effectiveness of the Combined Inhibition of EGFR and MET in EGFR-Mutant Non-Small-Cell Lung Cancer After Development of EGFR-TKI Resistance
BackgroundMET proto-oncogene amplification (amp) is an important mechanism underlying acquired resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). However, the optimal treatment strategy after acquiring MET-amp-mediated EGFR-TKI resistance remains controversial....
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-10-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2021.722039/full |
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doaj-2db165c15a7a49cab4ae9ffbb78232c5 |
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| record_format |
Article |
| collection |
DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
Li Liu Jingjing Qu Jianfu Heng Jianfu Heng Chunhua Zhou Yi Xiong Yi Xiong Haiyan Yang Wenjuan Jiang Liang Zeng Songlin Zhu Yongchang Zhang Jiarong Tan Chengping Hu Pengbo Deng Nong Yang |
| spellingShingle |
Li Liu Jingjing Qu Jianfu Heng Jianfu Heng Chunhua Zhou Yi Xiong Yi Xiong Haiyan Yang Wenjuan Jiang Liang Zeng Songlin Zhu Yongchang Zhang Jiarong Tan Chengping Hu Pengbo Deng Nong Yang A Large Real-World Study on the Effectiveness of the Combined Inhibition of EGFR and MET in EGFR-Mutant Non-Small-Cell Lung Cancer After Development of EGFR-TKI Resistance Frontiers in Oncology EGFR mutation MET amplification EGFR-TKI and crizotinib combination NSCLC EGFR-TKI resistance |
| author_facet |
Li Liu Jingjing Qu Jianfu Heng Jianfu Heng Chunhua Zhou Yi Xiong Yi Xiong Haiyan Yang Wenjuan Jiang Liang Zeng Songlin Zhu Yongchang Zhang Jiarong Tan Chengping Hu Pengbo Deng Nong Yang |
| author_sort |
Li Liu |
| title |
A Large Real-World Study on the Effectiveness of the Combined Inhibition of EGFR and MET in EGFR-Mutant Non-Small-Cell Lung Cancer After Development of EGFR-TKI Resistance |
| title_short |
A Large Real-World Study on the Effectiveness of the Combined Inhibition of EGFR and MET in EGFR-Mutant Non-Small-Cell Lung Cancer After Development of EGFR-TKI Resistance |
| title_full |
A Large Real-World Study on the Effectiveness of the Combined Inhibition of EGFR and MET in EGFR-Mutant Non-Small-Cell Lung Cancer After Development of EGFR-TKI Resistance |
| title_fullStr |
A Large Real-World Study on the Effectiveness of the Combined Inhibition of EGFR and MET in EGFR-Mutant Non-Small-Cell Lung Cancer After Development of EGFR-TKI Resistance |
| title_full_unstemmed |
A Large Real-World Study on the Effectiveness of the Combined Inhibition of EGFR and MET in EGFR-Mutant Non-Small-Cell Lung Cancer After Development of EGFR-TKI Resistance |
| title_sort |
large real-world study on the effectiveness of the combined inhibition of egfr and met in egfr-mutant non-small-cell lung cancer after development of egfr-tki resistance |
| publisher |
Frontiers Media S.A. |
| series |
Frontiers in Oncology |
| issn |
2234-943X |
| publishDate |
2021-10-01 |
| description |
BackgroundMET proto-oncogene amplification (amp) is an important mechanism underlying acquired resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). However, the optimal treatment strategy after acquiring MET-amp-mediated EGFR-TKI resistance remains controversial. Our study compared three treatment strategies for patients with EGFR-mutant non-small-cell lung cancer (NSCLC) who were detected with MET-amp at EGFR-TKI progression using next-generation sequencing.MethodsOf the 70 patients included in the study, 38 received EGFR-TKI + crizotinib, 10 received crizotinib monotherapy, and 22 received chemotherapy. Clinical outcomes and molecular profiles were analyzed.ResultsThe objective response rate was 48.6% for EGFR-TKI + crizotinib group, 40.0% for crizotinib monotherapy group, and 18.2% for chemotherapy group. Patients who received EGFR-TKI + crizotinib had significantly longer progression-free survival than those who received crizotinib or chemotherapy (5.0 vs. 2.3 vs. 2.9 months, p = 0.010), but overall survival was comparable (10.0 vs. 4.1 vs. 8.5 months, p = 0.088). TP53 mutation (58.5%) and EGFR-amp (42.9%) were frequent concurrent mutations of the cohort. Progression-free survival was significantly longer for patients with either concurrent TP53 mutation (n = 17) (6.0 vs. 2.3 vs. 2.9 months, p = 0.009) or EGFR-amp (n = 13) (5.0 vs. 1.2 vs. 2.4 months, p = 0.016) in the EGFR-TKI + crizotinib group than the other two regimen. Potential acquired resistance mechanisms to EGFR-TKI + crizotinib included EGFR-T790M (n = 2), EGFR-L718Q (n = 1), EGFR-S645C (n = 1), MET-D1228H (n = 1), BRAF-V600E (n = 1), NRAS-Q61H (n = 1), KRAS-amp (n = 1), ERBB2-amp (n = 1), CDK4-amp (n = 1), and MYC-amp (n = 1).ConclusionOur study provides real-world clinical evidence from a large cohort that simultaneous inhibition of EGFR and MET could be a more effective therapeutic strategy for patients with MET-amp acquired from EGFR-TKI therapy. |
| topic |
EGFR mutation MET amplification EGFR-TKI and crizotinib combination NSCLC EGFR-TKI resistance |
| url |
https://www.frontiersin.org/articles/10.3389/fonc.2021.722039/full |
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doaj-2db165c15a7a49cab4ae9ffbb78232c52021-10-01T04:37:31ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2021-10-011110.3389/fonc.2021.722039722039A Large Real-World Study on the Effectiveness of the Combined Inhibition of EGFR and MET in EGFR-Mutant Non-Small-Cell Lung Cancer After Development of EGFR-TKI ResistanceLi Liu0Jingjing Qu1Jianfu Heng2Jianfu Heng3Chunhua Zhou4Yi Xiong5Yi Xiong6Haiyan Yang7Wenjuan Jiang8Liang Zeng9Songlin Zhu10Yongchang Zhang11Jiarong Tan12Chengping Hu13Pengbo Deng14Nong Yang15Department of Lung Cancer and Gastroenterology, Hunan Cancer Hospital, Affiliated Tumor Hospital of Xiangya Medical School of Central South University, Changsha, ChinaDepartment of Respiratory Disease, Thoracic Disease Centre, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, ChinaDepartment of Lung Cancer and Gastroenterology, Hunan Cancer Hospital, Affiliated Tumor Hospital of Xiangya Medical School of Central South University, Changsha, ChinaDepartment of Clinical Pharmaceutical Research Institution, Hunan Cancer Hospital, Affiliated Tumor Hospital of Xiangya Medical School of Central South University, Changsha, ChinaDepartment of Lung Cancer and Gastroenterology, Hunan Cancer Hospital, Affiliated Tumor Hospital of Xiangya Medical School of Central South University, Changsha, ChinaDepartment of Lung Cancer and Gastroenterology, Hunan Cancer Hospital, Affiliated Tumor Hospital of Xiangya Medical School of Central South University, Changsha, ChinaDepartment of Clinical Pharmaceutical Research Institution, Hunan Cancer Hospital, Affiliated Tumor Hospital of Xiangya Medical School of Central South University, Changsha, ChinaDepartment of Lung Cancer and Gastroenterology, Hunan Cancer Hospital, Affiliated Tumor Hospital of Xiangya Medical School of Central South University, Changsha, ChinaDepartment of Lung Cancer and Gastroenterology, Hunan Cancer Hospital, Affiliated Tumor Hospital of Xiangya Medical School of Central South University, Changsha, ChinaDepartment of Lung Cancer and Gastroenterology, Hunan Cancer Hospital, Affiliated Tumor Hospital of Xiangya Medical School of Central South University, Changsha, ChinaDepartment of Clinical Pharmaceutical Research Institution, Hunan Cancer Hospital, Affiliated Tumor Hospital of Xiangya Medical School of Central South University, Changsha, ChinaDepartment of Lung Cancer and Gastroenterology, Hunan Cancer Hospital, Affiliated Tumor Hospital of Xiangya Medical School of Central South University, Changsha, ChinaDepartment of Respiratory Medicine, Xiangya Hospital of Central South University, Changsha, ChinaDepartment of Respiratory Medicine, Xiangya Hospital of Central South University, Changsha, ChinaDepartment of Respiratory Medicine, Xiangya Hospital of Central South University, Changsha, ChinaDepartment of Lung Cancer and Gastroenterology, Hunan Cancer Hospital, Affiliated Tumor Hospital of Xiangya Medical School of Central South University, Changsha, ChinaBackgroundMET proto-oncogene amplification (amp) is an important mechanism underlying acquired resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). However, the optimal treatment strategy after acquiring MET-amp-mediated EGFR-TKI resistance remains controversial. Our study compared three treatment strategies for patients with EGFR-mutant non-small-cell lung cancer (NSCLC) who were detected with MET-amp at EGFR-TKI progression using next-generation sequencing.MethodsOf the 70 patients included in the study, 38 received EGFR-TKI + crizotinib, 10 received crizotinib monotherapy, and 22 received chemotherapy. Clinical outcomes and molecular profiles were analyzed.ResultsThe objective response rate was 48.6% for EGFR-TKI + crizotinib group, 40.0% for crizotinib monotherapy group, and 18.2% for chemotherapy group. Patients who received EGFR-TKI + crizotinib had significantly longer progression-free survival than those who received crizotinib or chemotherapy (5.0 vs. 2.3 vs. 2.9 months, p = 0.010), but overall survival was comparable (10.0 vs. 4.1 vs. 8.5 months, p = 0.088). TP53 mutation (58.5%) and EGFR-amp (42.9%) were frequent concurrent mutations of the cohort. Progression-free survival was significantly longer for patients with either concurrent TP53 mutation (n = 17) (6.0 vs. 2.3 vs. 2.9 months, p = 0.009) or EGFR-amp (n = 13) (5.0 vs. 1.2 vs. 2.4 months, p = 0.016) in the EGFR-TKI + crizotinib group than the other two regimen. Potential acquired resistance mechanisms to EGFR-TKI + crizotinib included EGFR-T790M (n = 2), EGFR-L718Q (n = 1), EGFR-S645C (n = 1), MET-D1228H (n = 1), BRAF-V600E (n = 1), NRAS-Q61H (n = 1), KRAS-amp (n = 1), ERBB2-amp (n = 1), CDK4-amp (n = 1), and MYC-amp (n = 1).ConclusionOur study provides real-world clinical evidence from a large cohort that simultaneous inhibition of EGFR and MET could be a more effective therapeutic strategy for patients with MET-amp acquired from EGFR-TKI therapy.https://www.frontiersin.org/articles/10.3389/fonc.2021.722039/fullEGFR mutationMET amplificationEGFR-TKI and crizotinib combinationNSCLCEGFR-TKI resistance |