First-Line Osimertinib in Patients With EGFR-Mutated Non-Small Cell Lung Cancer: Effectiveness, Resistance Mechanisms, and Prognosis of Different Subsequent Treatments
Background: Although the clinical application of osimertinib, a third-generation epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI), has been a new step forward in the first-line treatment of non-small cell lung cancer (NSCLC), an increasing number of patients with progression on...
| Main Authors: | , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
SAGE Publishing
2022-11-01
|
| Series: | Clinical Medicine Insights: Oncology |
| Online Access: | https://doi.org/10.1177/11795549221134735 |
| _version_ | 1811230874272792576 |
|---|---|
| author | Naifu Nie Jianghua Li Jian Zhang Jie Dai Zhulin Liu Zhenyu Ding Yubo Wang Mengxiao Zhu Chen Hu Rui Han Huan Tang Li Li Yong He |
| author_facet | Naifu Nie Jianghua Li Jian Zhang Jie Dai Zhulin Liu Zhenyu Ding Yubo Wang Mengxiao Zhu Chen Hu Rui Han Huan Tang Li Li Yong He |
| author_sort | Naifu Nie |
| collection | DOAJ |
| description | Background: Although the clinical application of osimertinib, a third-generation epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI), has been a new step forward in the first-line treatment of non-small cell lung cancer (NSCLC), an increasing number of patients with progression on osimertinib represents a great challenge clinically. The patterns of resistance mechanisms and subsequent treatment strategies after first-line osimertinib resistance are not well established. Methods: Between January 1, 2016 and October 31, 2020, a consecutive of 56 EGFR-mutant lung cancer patients treated with osimertinib as first-line therapy at Daping Hospital (Chongqing, China) were retrospective screened. The samples of pre-osimertinib and osimertinib-resistance were all detected by next-generation sequencing (NGS) panels. Statistical analyses were carried out using SPSS 23.0 software. Survival analyses were performed using the Kaplan–Meier method and compared using a log-rank test between groups. Results: Among 47 patients with osimertinib effectiveness analysis, the median progression free survival (mPFS) was 15.4 months (95% confidence interval [CI]: 12.2-24.9 months), and median overall survival (mOS) was 35.5 months (95% CI: 23.9 months -NA). A total of 21 patients underwent repeated NGS tests upon osimertinib resistance. MET amplification was the most common resistance mechanism (6/21, 28.6%), followed by C797S mutation (5/21, 23.8%). A total of 15 patients received subsequent treatments, with mPFS of 7.3 months (95% CI 5.0 months -NA). Among them, 7 patients with EGFR C797 S or/and MET amplification received subsequent second-line targeted therapy, achieving mPFS of 7.3 months (95% CI 4.5 months -NA). Of note, 3 patients received immunotherapy as second- or third-line treatment after osimertinib resistance, achieving median clinical benefit of 37.3 months. Conclusions: MET amplification and C797S mutation are main resistance mechanisms, which could be targeted by crizotinib and gefitinib, respectively. More than 50% patients could receive subsequent anticancer targetable therapies after first-line osimertinib resistance. Immunotherapy may also be an acceptable choice after osimertinib resistance. |
| first_indexed | 2024-04-12T10:35:27Z |
| format | Article |
| id | doaj.art-06ff200363b7492fa950dee683d1d333 |
| institution | Directory Open Access Journal |
| issn | 1179-5549 |
| language | English |
| last_indexed | 2024-04-12T10:35:27Z |
| publishDate | 2022-11-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Clinical Medicine Insights: Oncology |
| spelling | doaj.art-06ff200363b7492fa950dee683d1d3332022-12-22T03:36:43ZengSAGE PublishingClinical Medicine Insights: Oncology1179-55492022-11-011610.1177/11795549221134735First-Line Osimertinib in Patients With EGFR-Mutated Non-Small Cell Lung Cancer: Effectiveness, Resistance Mechanisms, and Prognosis of Different Subsequent TreatmentsNaifu Nie0Jianghua Li1Jian Zhang2Jie Dai3Zhulin Liu4Zhenyu Ding5Yubo Wang6Mengxiao Zhu7Chen Hu8Rui Han9Huan Tang10Li Li11Yong He12Department of Respiratory Medicine, Daping Hospital, Army Medical University, Chongqing, P.R. ChinaDepartment of Respiratory Medicine, Daping Hospital, Army Medical University, Chongqing, P.R. ChinaDepartment of Respiratory Medicine, Daping Hospital, Army Medical University, Chongqing, P.R. ChinaDepartment of Respiratory Medicine, Daping Hospital, Army Medical University, Chongqing, P.R. ChinaDepartment of Respiratory Medicine, Daping Hospital, Army Medical University, Chongqing, P.R. ChinaDepartment of Thoracic Oncology, West China Hospital of Sichuan University, Sichuan, P.R. ChinaDepartment of Respiratory Medicine, Daping Hospital, Army Medical University, Chongqing, P.R. ChinaDepartment of Respiratory Medicine, Daping Hospital, Army Medical University, Chongqing, P.R. ChinaDepartment of Respiratory Medicine, Daping Hospital, Army Medical University, Chongqing, P.R. ChinaDepartment of Respiratory Medicine, Daping Hospital, Army Medical University, Chongqing, P.R. ChinaDepartment of Respiratory Medicine, Daping Hospital, Army Medical University, Chongqing, P.R. ChinaDepartment of Respiratory Medicine, Daping Hospital, Army Medical University, Chongqing, P.R. ChinaDepartment of Respiratory Medicine, Daping Hospital, Army Medical University, Chongqing, P.R. ChinaBackground: Although the clinical application of osimertinib, a third-generation epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI), has been a new step forward in the first-line treatment of non-small cell lung cancer (NSCLC), an increasing number of patients with progression on osimertinib represents a great challenge clinically. The patterns of resistance mechanisms and subsequent treatment strategies after first-line osimertinib resistance are not well established. Methods: Between January 1, 2016 and October 31, 2020, a consecutive of 56 EGFR-mutant lung cancer patients treated with osimertinib as first-line therapy at Daping Hospital (Chongqing, China) were retrospective screened. The samples of pre-osimertinib and osimertinib-resistance were all detected by next-generation sequencing (NGS) panels. Statistical analyses were carried out using SPSS 23.0 software. Survival analyses were performed using the Kaplan–Meier method and compared using a log-rank test between groups. Results: Among 47 patients with osimertinib effectiveness analysis, the median progression free survival (mPFS) was 15.4 months (95% confidence interval [CI]: 12.2-24.9 months), and median overall survival (mOS) was 35.5 months (95% CI: 23.9 months -NA). A total of 21 patients underwent repeated NGS tests upon osimertinib resistance. MET amplification was the most common resistance mechanism (6/21, 28.6%), followed by C797S mutation (5/21, 23.8%). A total of 15 patients received subsequent treatments, with mPFS of 7.3 months (95% CI 5.0 months -NA). Among them, 7 patients with EGFR C797 S or/and MET amplification received subsequent second-line targeted therapy, achieving mPFS of 7.3 months (95% CI 4.5 months -NA). Of note, 3 patients received immunotherapy as second- or third-line treatment after osimertinib resistance, achieving median clinical benefit of 37.3 months. Conclusions: MET amplification and C797S mutation are main resistance mechanisms, which could be targeted by crizotinib and gefitinib, respectively. More than 50% patients could receive subsequent anticancer targetable therapies after first-line osimertinib resistance. Immunotherapy may also be an acceptable choice after osimertinib resistance.https://doi.org/10.1177/11795549221134735 |
| spellingShingle | Naifu Nie Jianghua Li Jian Zhang Jie Dai Zhulin Liu Zhenyu Ding Yubo Wang Mengxiao Zhu Chen Hu Rui Han Huan Tang Li Li Yong He First-Line Osimertinib in Patients With EGFR-Mutated Non-Small Cell Lung Cancer: Effectiveness, Resistance Mechanisms, and Prognosis of Different Subsequent Treatments Clinical Medicine Insights: Oncology |
| title | First-Line Osimertinib in Patients With EGFR-Mutated Non-Small Cell Lung Cancer: Effectiveness, Resistance Mechanisms, and Prognosis of Different Subsequent Treatments |
| title_full | First-Line Osimertinib in Patients With EGFR-Mutated Non-Small Cell Lung Cancer: Effectiveness, Resistance Mechanisms, and Prognosis of Different Subsequent Treatments |
| title_fullStr | First-Line Osimertinib in Patients With EGFR-Mutated Non-Small Cell Lung Cancer: Effectiveness, Resistance Mechanisms, and Prognosis of Different Subsequent Treatments |
| title_full_unstemmed | First-Line Osimertinib in Patients With EGFR-Mutated Non-Small Cell Lung Cancer: Effectiveness, Resistance Mechanisms, and Prognosis of Different Subsequent Treatments |
| title_short | First-Line Osimertinib in Patients With EGFR-Mutated Non-Small Cell Lung Cancer: Effectiveness, Resistance Mechanisms, and Prognosis of Different Subsequent Treatments |
| title_sort | first line osimertinib in patients with egfr mutated non small cell lung cancer effectiveness resistance mechanisms and prognosis of different subsequent treatments |
| url | https://doi.org/10.1177/11795549221134735 |
| work_keys_str_mv | AT naifunie firstlineosimertinibinpatientswithegfrmutatednonsmallcelllungcancereffectivenessresistancemechanismsandprognosisofdifferentsubsequenttreatments AT jianghuali firstlineosimertinibinpatientswithegfrmutatednonsmallcelllungcancereffectivenessresistancemechanismsandprognosisofdifferentsubsequenttreatments AT jianzhang firstlineosimertinibinpatientswithegfrmutatednonsmallcelllungcancereffectivenessresistancemechanismsandprognosisofdifferentsubsequenttreatments AT jiedai firstlineosimertinibinpatientswithegfrmutatednonsmallcelllungcancereffectivenessresistancemechanismsandprognosisofdifferentsubsequenttreatments AT zhulinliu firstlineosimertinibinpatientswithegfrmutatednonsmallcelllungcancereffectivenessresistancemechanismsandprognosisofdifferentsubsequenttreatments AT zhenyuding firstlineosimertinibinpatientswithegfrmutatednonsmallcelllungcancereffectivenessresistancemechanismsandprognosisofdifferentsubsequenttreatments AT yubowang firstlineosimertinibinpatientswithegfrmutatednonsmallcelllungcancereffectivenessresistancemechanismsandprognosisofdifferentsubsequenttreatments AT mengxiaozhu firstlineosimertinibinpatientswithegfrmutatednonsmallcelllungcancereffectivenessresistancemechanismsandprognosisofdifferentsubsequenttreatments AT chenhu firstlineosimertinibinpatientswithegfrmutatednonsmallcelllungcancereffectivenessresistancemechanismsandprognosisofdifferentsubsequenttreatments AT ruihan firstlineosimertinibinpatientswithegfrmutatednonsmallcelllungcancereffectivenessresistancemechanismsandprognosisofdifferentsubsequenttreatments AT huantang firstlineosimertinibinpatientswithegfrmutatednonsmallcelllungcancereffectivenessresistancemechanismsandprognosisofdifferentsubsequenttreatments AT lili firstlineosimertinibinpatientswithegfrmutatednonsmallcelllungcancereffectivenessresistancemechanismsandprognosisofdifferentsubsequenttreatments AT yonghe firstlineosimertinibinpatientswithegfrmutatednonsmallcelllungcancereffectivenessresistancemechanismsandprognosisofdifferentsubsequenttreatments |