Sequential treatment in advanced non–small cell lung cancer harboring EGFR mutations
Background: Epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) are standard treatments for advanced EGFR-mutated non–small cell lung cancer (NSCLC) patients. Osimertinib is an effective therapy for NSCLC patients with acquired resistance due to T790M mutation after first- and...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
SAGE Publishing
2022-10-01
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| Series: | Therapeutic Advances in Respiratory Disease |
| Online Access: | https://doi.org/10.1177/17534666221132731 |
| _version_ | 1797853291193827328 |
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| author | Ping-Chih Hsu John Wen-Cheng Chang Ching-Fu Chang Chen-Yang Huang Cheng-Ta Yang Chih-Hsi Scott Kuo Yueh-Fu Fang Chiao-En Wu |
| author_facet | Ping-Chih Hsu John Wen-Cheng Chang Ching-Fu Chang Chen-Yang Huang Cheng-Ta Yang Chih-Hsi Scott Kuo Yueh-Fu Fang Chiao-En Wu |
| author_sort | Ping-Chih Hsu |
| collection | DOAJ |
| description | Background: Epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) are standard treatments for advanced EGFR-mutated non–small cell lung cancer (NSCLC) patients. Osimertinib is an effective therapy for NSCLC patients with acquired resistance due to T790M mutation after first- and second-generation EGFR-TKI treatment. This study aimed to analyze the clinical outcomes of sequential therapy following first-line EGFR-TKIs and the predictive factors of an acquired T790M mutation. Methods: Between January 2014 and December 2018, data from 2190 advanced NSCLC patients with common EGFR mutations (exon 19 deletion and L858R) receiving first- and second-generation EGFR-TKIs in Linkou, Kaohsiung, Chiayi and Keelung Chang Gung Memorial Hospitals were retrospectively retrieved and analyzed. Results: Until August 2021, among 1943 patients who experienced progressive disease, 526 underwent T790M mutation tests, and their T790M-positive rate was 53.6%. Exon 19 deletion mutation and progression-free survival (PFS) of >12 months were positively associated with secondary T790M mutation. Different first-line first- and second-generation EGFR-TKI therapies did not affect the appearance of acquired T790M mutations. The median overall survival (OS) was 58.3 [95% confidence interval (CI): 49.0–67.5] months among the patients with T790M mutation who received second-line osimertinib therapy compared with 31.0 (95% CI: 27.5–34.5) months among the patients without T790M mutation who received chemotherapy alone. The multivariate analysis showed that a poor performance status (score: >2), nonadenocarcinoma histology, stage IV cancer, liver metastasis, brain metastasis, PFS while on first-line EGFR-TKIs, and subsequent chemotherapy without third-generation EGFR-TKIs were significant independent unfavorable prognostic factors for OS. Conclusion: This study demonstrated the efficacy of first-line EGFR-TKIs and sequential osimertinib therapy. The results of our study suggest that T790M mutation tests are important for the use of subsequent osimertinib, which yielded favorable survival outcomes. |
| first_indexed | 2024-04-09T19:47:10Z |
| format | Article |
| id | doaj.art-00f4c4be18244e979f2f334047c74e95 |
| institution | Directory Open Access Journal |
| issn | 1753-4666 |
| language | English |
| last_indexed | 2024-04-09T19:47:10Z |
| publishDate | 2022-10-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Therapeutic Advances in Respiratory Disease |
| spelling | doaj.art-00f4c4be18244e979f2f334047c74e952023-04-03T13:33:35ZengSAGE PublishingTherapeutic Advances in Respiratory Disease1753-46662022-10-011610.1177/17534666221132731Sequential treatment in advanced non–small cell lung cancer harboring EGFR mutationsPing-Chih HsuJohn Wen-Cheng ChangChing-Fu ChangChen-Yang HuangCheng-Ta YangChih-Hsi Scott KuoYueh-Fu FangChiao-En WuBackground: Epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) are standard treatments for advanced EGFR-mutated non–small cell lung cancer (NSCLC) patients. Osimertinib is an effective therapy for NSCLC patients with acquired resistance due to T790M mutation after first- and second-generation EGFR-TKI treatment. This study aimed to analyze the clinical outcomes of sequential therapy following first-line EGFR-TKIs and the predictive factors of an acquired T790M mutation. Methods: Between January 2014 and December 2018, data from 2190 advanced NSCLC patients with common EGFR mutations (exon 19 deletion and L858R) receiving first- and second-generation EGFR-TKIs in Linkou, Kaohsiung, Chiayi and Keelung Chang Gung Memorial Hospitals were retrospectively retrieved and analyzed. Results: Until August 2021, among 1943 patients who experienced progressive disease, 526 underwent T790M mutation tests, and their T790M-positive rate was 53.6%. Exon 19 deletion mutation and progression-free survival (PFS) of >12 months were positively associated with secondary T790M mutation. Different first-line first- and second-generation EGFR-TKI therapies did not affect the appearance of acquired T790M mutations. The median overall survival (OS) was 58.3 [95% confidence interval (CI): 49.0–67.5] months among the patients with T790M mutation who received second-line osimertinib therapy compared with 31.0 (95% CI: 27.5–34.5) months among the patients without T790M mutation who received chemotherapy alone. The multivariate analysis showed that a poor performance status (score: >2), nonadenocarcinoma histology, stage IV cancer, liver metastasis, brain metastasis, PFS while on first-line EGFR-TKIs, and subsequent chemotherapy without third-generation EGFR-TKIs were significant independent unfavorable prognostic factors for OS. Conclusion: This study demonstrated the efficacy of first-line EGFR-TKIs and sequential osimertinib therapy. The results of our study suggest that T790M mutation tests are important for the use of subsequent osimertinib, which yielded favorable survival outcomes.https://doi.org/10.1177/17534666221132731 |
| spellingShingle | Ping-Chih Hsu John Wen-Cheng Chang Ching-Fu Chang Chen-Yang Huang Cheng-Ta Yang Chih-Hsi Scott Kuo Yueh-Fu Fang Chiao-En Wu Sequential treatment in advanced non–small cell lung cancer harboring EGFR mutations Therapeutic Advances in Respiratory Disease |
| title | Sequential treatment in advanced non–small cell lung cancer harboring EGFR mutations |
| title_full | Sequential treatment in advanced non–small cell lung cancer harboring EGFR mutations |
| title_fullStr | Sequential treatment in advanced non–small cell lung cancer harboring EGFR mutations |
| title_full_unstemmed | Sequential treatment in advanced non–small cell lung cancer harboring EGFR mutations |
| title_short | Sequential treatment in advanced non–small cell lung cancer harboring EGFR mutations |
| title_sort | sequential treatment in advanced non small cell lung cancer harboring egfr mutations |
| url | https://doi.org/10.1177/17534666221132731 |
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