Differential prognostic value of tumor and plasma T790M mutations in EGFR TKI-treated advanced NSCLC
Background: Substitution of methionine for threonine at codon 790 (T790M) of epidermal growth factor receptor (EGFR) represents the major mechanism of resistance to EGFR tyrosine kinase inhibitors (TKIs) in EGFR -mutant non-small-cell lung cancer. We determined the prognostic impact and association...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
SAGE Publishing
2024-01-01
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| Series: | Therapeutic Advances in Medical Oncology |
| Online Access: | https://doi.org/10.1177/17588359231222604 |
| _version_ | 1827378082489565184 |
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| author | Pi-Hung Tung Tzu-Hsuan Chiu Allen Chung-Cheng Huang Jia-Shiuan Ju Chi-Hsien Huang Chin-Chou Wang How-Wen Ko Fu-Tsai Chung Ping-Chih Hsu Yueh-Fu Fang Yi-Ke Guo Chih-Hsi Scott Kuo Cheng-Ta Yang |
| author_facet | Pi-Hung Tung Tzu-Hsuan Chiu Allen Chung-Cheng Huang Jia-Shiuan Ju Chi-Hsien Huang Chin-Chou Wang How-Wen Ko Fu-Tsai Chung Ping-Chih Hsu Yueh-Fu Fang Yi-Ke Guo Chih-Hsi Scott Kuo Cheng-Ta Yang |
| author_sort | Pi-Hung Tung |
| collection | DOAJ |
| description | Background: Substitution of methionine for threonine at codon 790 (T790M) of epidermal growth factor receptor (EGFR) represents the major mechanism of resistance to EGFR tyrosine kinase inhibitors (TKIs) in EGFR -mutant non-small-cell lung cancer. We determined the prognostic impact and association of secondary T790M mutations with the outcomes of osimertinib and chemotherapy. Methods: Patients (n = 460) progressing from first-line EGFR-TKI treatment were assessed. Tissue and/or liquid biopsies were used to determine T790M status; post-progression overall survival (OS) was analyzed. Results: Overall, 143 (31.1%) patients were T790M positive, 95 (20.7%) were T790M negative, and 222 (48.2%) had unknown T790M status. T790M status [T790M positive versus T790M negative: hazard ratio (HR) 0.48 (95% confidence interval (CI), 0.32–0.70); p < 0.001, T790M unknown versus T790M negative: HR 1.97 (95% CI, 1.47–2.64); p < 0.001] was significantly associated with post-progression OS. T790M positivity rates were similar for tissue (90/168, 53.6%) and liquid (53/90, 58.9%) biopsies (Fisher’s exact test, p = 0.433). Tumor T790M-positive patients had significantly longer post-progression OS than tumor T790M-negative patients (34.1 versus 17.1 months; log-rank test, p = 8 × 10 −5 ). Post-progression OS was similar between plasma T790M-positive and -negative patients (17.4 versus not reached; log-rank test, p = 0.600). In tumor T790M-positive patients, post-progression OS was similar after osimertinib and chemotherapy [34.1 versus 29.1 months; log-rank test, p = 0.900; HR 1.06 (95% CI, 0.44–2.57); p = 0.897]. Conclusion: T790M positivity predicts better post-progression OS than T790M negativity; tumor T790M positivity has a stronger prognostic impact than plasma T790M positivity. Osimertinib and chemotherapy provide similar OS benefits in patients with T790M-positive tumors. |
| first_indexed | 2024-03-08T12:49:24Z |
| format | Article |
| id | doaj.art-cb59f58b72a54d5aa11a70e91bdabd7a |
| institution | Directory Open Access Journal |
| issn | 1758-8359 |
| language | English |
| last_indexed | 2024-03-08T12:49:24Z |
| publishDate | 2024-01-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Therapeutic Advances in Medical Oncology |
| spelling | doaj.art-cb59f58b72a54d5aa11a70e91bdabd7a2024-01-20T11:04:17ZengSAGE PublishingTherapeutic Advances in Medical Oncology1758-83592024-01-011610.1177/17588359231222604Differential prognostic value of tumor and plasma T790M mutations in EGFR TKI-treated advanced NSCLCPi-Hung TungTzu-Hsuan ChiuAllen Chung-Cheng HuangJia-Shiuan JuChi-Hsien HuangChin-Chou WangHow-Wen KoFu-Tsai ChungPing-Chih HsuYueh-Fu FangYi-Ke GuoChih-Hsi Scott KuoCheng-Ta YangBackground: Substitution of methionine for threonine at codon 790 (T790M) of epidermal growth factor receptor (EGFR) represents the major mechanism of resistance to EGFR tyrosine kinase inhibitors (TKIs) in EGFR -mutant non-small-cell lung cancer. We determined the prognostic impact and association of secondary T790M mutations with the outcomes of osimertinib and chemotherapy. Methods: Patients (n = 460) progressing from first-line EGFR-TKI treatment were assessed. Tissue and/or liquid biopsies were used to determine T790M status; post-progression overall survival (OS) was analyzed. Results: Overall, 143 (31.1%) patients were T790M positive, 95 (20.7%) were T790M negative, and 222 (48.2%) had unknown T790M status. T790M status [T790M positive versus T790M negative: hazard ratio (HR) 0.48 (95% confidence interval (CI), 0.32–0.70); p < 0.001, T790M unknown versus T790M negative: HR 1.97 (95% CI, 1.47–2.64); p < 0.001] was significantly associated with post-progression OS. T790M positivity rates were similar for tissue (90/168, 53.6%) and liquid (53/90, 58.9%) biopsies (Fisher’s exact test, p = 0.433). Tumor T790M-positive patients had significantly longer post-progression OS than tumor T790M-negative patients (34.1 versus 17.1 months; log-rank test, p = 8 × 10 −5 ). Post-progression OS was similar between plasma T790M-positive and -negative patients (17.4 versus not reached; log-rank test, p = 0.600). In tumor T790M-positive patients, post-progression OS was similar after osimertinib and chemotherapy [34.1 versus 29.1 months; log-rank test, p = 0.900; HR 1.06 (95% CI, 0.44–2.57); p = 0.897]. Conclusion: T790M positivity predicts better post-progression OS than T790M negativity; tumor T790M positivity has a stronger prognostic impact than plasma T790M positivity. Osimertinib and chemotherapy provide similar OS benefits in patients with T790M-positive tumors.https://doi.org/10.1177/17588359231222604 |
| spellingShingle | Pi-Hung Tung Tzu-Hsuan Chiu Allen Chung-Cheng Huang Jia-Shiuan Ju Chi-Hsien Huang Chin-Chou Wang How-Wen Ko Fu-Tsai Chung Ping-Chih Hsu Yueh-Fu Fang Yi-Ke Guo Chih-Hsi Scott Kuo Cheng-Ta Yang Differential prognostic value of tumor and plasma T790M mutations in EGFR TKI-treated advanced NSCLC Therapeutic Advances in Medical Oncology |
| title | Differential prognostic value of tumor and plasma T790M mutations in EGFR TKI-treated advanced NSCLC |
| title_full | Differential prognostic value of tumor and plasma T790M mutations in EGFR TKI-treated advanced NSCLC |
| title_fullStr | Differential prognostic value of tumor and plasma T790M mutations in EGFR TKI-treated advanced NSCLC |
| title_full_unstemmed | Differential prognostic value of tumor and plasma T790M mutations in EGFR TKI-treated advanced NSCLC |
| title_short | Differential prognostic value of tumor and plasma T790M mutations in EGFR TKI-treated advanced NSCLC |
| title_sort | differential prognostic value of tumor and plasma t790m mutations in egfr tki treated advanced nsclc |
| url | https://doi.org/10.1177/17588359231222604 |
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