Combination of EGFR-TKIs and chemotherapy as first-line therapy for advanced NSCLC: a meta-analysis.
The impact of combining epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) and chemotherapy as first-line therapy for patients with advanced non-small-cell lung cancer (NSCLC) remains controversial. Therefore, randomized trials that compared this combined regimen with chemothera...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3827342?pdf=render |
| _version_ | 1819236376979177472 |
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| author | Pu-Yun OuYang Zhen Su Yan-Ping Mao Wuguo Deng Fang-Yun Xie |
| author_facet | Pu-Yun OuYang Zhen Su Yan-Ping Mao Wuguo Deng Fang-Yun Xie |
| author_sort | Pu-Yun OuYang |
| collection | DOAJ |
| description | The impact of combining epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) and chemotherapy as first-line therapy for patients with advanced non-small-cell lung cancer (NSCLC) remains controversial. Therefore, randomized trials that compared this combined regimen with chemotherapy or EGFR-TKIs monotherapy were included for this meta-analysis. We used published hazard ratios (HRs), if available, or derived treatment estimates from other survival data. Pooled estimates of treatment efficacy of the combined regimen in the entire unselected population and selected patients by EGFR-mutation status and smoking history were calculated. Eight trials eventually entered into this meta-analysis, including 4585 patients. Overall, the combined regimen significantly delayed disease progression (HR = 0.81, 95% CI 0.69-0.95, P = 0.01); subgroup analysis showed significantly higher progression free survival advantages in Asian patients (P<0.001), with sequential combination of TKIs and chemotherapy (P = 0.02). In selected patients by EGFR-mutation, both mutation positive (HR = 0.48, 95% CI 0.28-0.83, P = 0.009) and negative (HR = 0.84, 95% CI 0.72-0.98, P = 0.02) patients gained progression free survival benefit from the combined regimen, albeit the magnitude of benefit was marginally larger in mutation positive patients (P = 0.05). In selected patients by smoking history, never/light smokers achieved a great progression free survival benefit from the combined regimen (HR = 0.51, 95% CI 0.35-0.74, P = 0.0004). Unfortunately, the combined regimen had no significant impact on overall survival, irrespective of ethnicity, dose schedules or EGFR-mutation status. Severe anorexia (RR = 2.01, 95% CI 1.11-3.63; P = 0.02) and diarrhea (RR = 2.70, 95% CI 1.94-3.76; P<0.001) were more frequent in the combined regimen arm. This strategy of combining EGFR-TKIs and chemotherapy deserved to be considered in the future, although it is not approved for advanced NSCLC at the moment. |
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| format | Article |
| id | doaj.art-c4d656bdab844e74ac5b2e85b490c01b |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-23T13:03:28Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-c4d656bdab844e74ac5b2e85b490c01b2022-12-21T17:45:57ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-01811e7900010.1371/journal.pone.0079000Combination of EGFR-TKIs and chemotherapy as first-line therapy for advanced NSCLC: a meta-analysis.Pu-Yun OuYangZhen SuYan-Ping MaoWuguo DengFang-Yun XieThe impact of combining epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) and chemotherapy as first-line therapy for patients with advanced non-small-cell lung cancer (NSCLC) remains controversial. Therefore, randomized trials that compared this combined regimen with chemotherapy or EGFR-TKIs monotherapy were included for this meta-analysis. We used published hazard ratios (HRs), if available, or derived treatment estimates from other survival data. Pooled estimates of treatment efficacy of the combined regimen in the entire unselected population and selected patients by EGFR-mutation status and smoking history were calculated. Eight trials eventually entered into this meta-analysis, including 4585 patients. Overall, the combined regimen significantly delayed disease progression (HR = 0.81, 95% CI 0.69-0.95, P = 0.01); subgroup analysis showed significantly higher progression free survival advantages in Asian patients (P<0.001), with sequential combination of TKIs and chemotherapy (P = 0.02). In selected patients by EGFR-mutation, both mutation positive (HR = 0.48, 95% CI 0.28-0.83, P = 0.009) and negative (HR = 0.84, 95% CI 0.72-0.98, P = 0.02) patients gained progression free survival benefit from the combined regimen, albeit the magnitude of benefit was marginally larger in mutation positive patients (P = 0.05). In selected patients by smoking history, never/light smokers achieved a great progression free survival benefit from the combined regimen (HR = 0.51, 95% CI 0.35-0.74, P = 0.0004). Unfortunately, the combined regimen had no significant impact on overall survival, irrespective of ethnicity, dose schedules or EGFR-mutation status. Severe anorexia (RR = 2.01, 95% CI 1.11-3.63; P = 0.02) and diarrhea (RR = 2.70, 95% CI 1.94-3.76; P<0.001) were more frequent in the combined regimen arm. This strategy of combining EGFR-TKIs and chemotherapy deserved to be considered in the future, although it is not approved for advanced NSCLC at the moment.http://europepmc.org/articles/PMC3827342?pdf=render |
| spellingShingle | Pu-Yun OuYang Zhen Su Yan-Ping Mao Wuguo Deng Fang-Yun Xie Combination of EGFR-TKIs and chemotherapy as first-line therapy for advanced NSCLC: a meta-analysis. PLoS ONE |
| title | Combination of EGFR-TKIs and chemotherapy as first-line therapy for advanced NSCLC: a meta-analysis. |
| title_full | Combination of EGFR-TKIs and chemotherapy as first-line therapy for advanced NSCLC: a meta-analysis. |
| title_fullStr | Combination of EGFR-TKIs and chemotherapy as first-line therapy for advanced NSCLC: a meta-analysis. |
| title_full_unstemmed | Combination of EGFR-TKIs and chemotherapy as first-line therapy for advanced NSCLC: a meta-analysis. |
| title_short | Combination of EGFR-TKIs and chemotherapy as first-line therapy for advanced NSCLC: a meta-analysis. |
| title_sort | combination of egfr tkis and chemotherapy as first line therapy for advanced nsclc a meta analysis |
| url | http://europepmc.org/articles/PMC3827342?pdf=render |
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