Comparative analysis of first-generation epidermal growth factor receptor inhibitors combined with chemotherapy versus third-generation epidermal growth factor receptor inhibitors in the treatment of advanced non-small cell lung cancer: a systematic review and meta-analysis
BackgroundIn advanced non-small cell lung cancer with EGFR mutations, third-generation EGFR TKIs (3rd-G TKIs) are currently the preferred first-line treatment. Previous studies have demonstrated that combining first-generation EGFR TKIs with chemotherapy (1st-G TKIs + chemo) also significantly enhan...
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Frontiers Media S.A.
2025-08-01
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2025.1586332/full |
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| author | Siyan Peng Siyan Peng Zhixin Yu Zhixin Yu Honglin Zhu Honglin Zhu Chuwen Liang Chuwen Liang Huijuan Qiu Huijuan Qiu Shaodong Hong Shaodong Hong Yixin Zhou Yixin Zhou |
| author_facet | Siyan Peng Siyan Peng Zhixin Yu Zhixin Yu Honglin Zhu Honglin Zhu Chuwen Liang Chuwen Liang Huijuan Qiu Huijuan Qiu Shaodong Hong Shaodong Hong Yixin Zhou Yixin Zhou |
| author_sort | Siyan Peng |
| collection | DOAJ |
| description | BackgroundIn advanced non-small cell lung cancer with EGFR mutations, third-generation EGFR TKIs (3rd-G TKIs) are currently the preferred first-line treatment. Previous studies have demonstrated that combining first-generation EGFR TKIs with chemotherapy (1st-G TKIs + chemo) also significantly enhances efficacy compared to 1st-G TKIs alone. This study aims to compare the effectiveness of 1st-G TKIs + chemo against 3rd-G TKIs.MethodsWe conducted an indirect meta-analysis of randomized controlled trials comparing 1st-G TKIs + chemo to 3rd-G TKIs. Randomized controlled trials (RCTs) were searched from the PubMed, Embase and Cochrane Library databases. Outcomes included progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and grade ≥3 treatment-related adverse events (TRAEs). Data were analyzed using inverse variance and Mantel-Haenszel methods.ResultsTen RCTs with 3,014 patients met the inclusion criteria. Direct comparisons indicated that 1st-G TKIs + chemo significantly improved PFS (HR 0.54, P < 0.001), OS (HR 0.62, P < 0.001), and ORR (RR 1.21, P < 0.001) compared to 1st-G TKIs alone. Indirect comparisons between 1st-G TKIs + chemo and 3rd-G TKIs revealed no significant differences in PFS (HR 1.17; 95% CI, 0.98 to 1.40; P = 0.075) or OS (HR 0.78; 95% CI, 0.56 to 1.07; P = 0.122). Although 1st-G TKIs + chemo showed a 16% improvement in ORR compared to 3rd-G TKIs (RR 1.16; 95% CI, 1.06 to 1.27; P < 0.001), it was also associated with a notable increase in grade ≥3 TRAEs (RR 2.41; 95% CI, 1.63 to 3.57; P < 0.001).Conclusion1st-G TKIs + chemo demonstrated PFS and OS comparable to 3rd-G TKIs. Moreover, 1st-G TKIs + chemo may be a viable option for patients who prioritize a higher response rate.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO/view/CRD42023461565 identifer, PROSPERO (CRD42023461565). |
| format | Article |
| id | doaj-art-acd8591b04f34cceb8631bf42d0f7b8b |
| institution | DOAJ |
| issn | 1663-9812 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Pharmacology |
| spelling | doaj-art-acd8591b04f34cceb8631bf42d0f7b8b2025-08-20T03:02:52ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122025-08-011610.3389/fphar.2025.15863321586332Comparative analysis of first-generation epidermal growth factor receptor inhibitors combined with chemotherapy versus third-generation epidermal growth factor receptor inhibitors in the treatment of advanced non-small cell lung cancer: a systematic review and meta-analysisSiyan Peng0Siyan Peng1Zhixin Yu2Zhixin Yu3Honglin Zhu4Honglin Zhu5Chuwen Liang6Chuwen Liang7Huijuan Qiu8Huijuan Qiu9Shaodong Hong10Shaodong Hong11Yixin Zhou12Yixin Zhou13State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, ChinaDepartment of VIP Region, Sun Yat-sen University Cancer Center, Guangzhou, ChinaState Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, ChinaDepartment of VIP Region, Sun Yat-sen University Cancer Center, Guangzhou, ChinaState Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, ChinaDepartment of VIP Region, Sun Yat-sen University Cancer Center, Guangzhou, ChinaState Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, ChinaDepartment of VIP Region, Sun Yat-sen University Cancer Center, Guangzhou, ChinaState Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, ChinaDepartment of VIP Region, Sun Yat-sen University Cancer Center, Guangzhou, ChinaState Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, ChinaDepartment of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, ChinaState Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, ChinaDepartment of VIP Region, Sun Yat-sen University Cancer Center, Guangzhou, ChinaBackgroundIn advanced non-small cell lung cancer with EGFR mutations, third-generation EGFR TKIs (3rd-G TKIs) are currently the preferred first-line treatment. Previous studies have demonstrated that combining first-generation EGFR TKIs with chemotherapy (1st-G TKIs + chemo) also significantly enhances efficacy compared to 1st-G TKIs alone. This study aims to compare the effectiveness of 1st-G TKIs + chemo against 3rd-G TKIs.MethodsWe conducted an indirect meta-analysis of randomized controlled trials comparing 1st-G TKIs + chemo to 3rd-G TKIs. Randomized controlled trials (RCTs) were searched from the PubMed, Embase and Cochrane Library databases. Outcomes included progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and grade ≥3 treatment-related adverse events (TRAEs). Data were analyzed using inverse variance and Mantel-Haenszel methods.ResultsTen RCTs with 3,014 patients met the inclusion criteria. Direct comparisons indicated that 1st-G TKIs + chemo significantly improved PFS (HR 0.54, P < 0.001), OS (HR 0.62, P < 0.001), and ORR (RR 1.21, P < 0.001) compared to 1st-G TKIs alone. Indirect comparisons between 1st-G TKIs + chemo and 3rd-G TKIs revealed no significant differences in PFS (HR 1.17; 95% CI, 0.98 to 1.40; P = 0.075) or OS (HR 0.78; 95% CI, 0.56 to 1.07; P = 0.122). Although 1st-G TKIs + chemo showed a 16% improvement in ORR compared to 3rd-G TKIs (RR 1.16; 95% CI, 1.06 to 1.27; P < 0.001), it was also associated with a notable increase in grade ≥3 TRAEs (RR 2.41; 95% CI, 1.63 to 3.57; P < 0.001).Conclusion1st-G TKIs + chemo demonstrated PFS and OS comparable to 3rd-G TKIs. Moreover, 1st-G TKIs + chemo may be a viable option for patients who prioritize a higher response rate.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO/view/CRD42023461565 identifer, PROSPERO (CRD42023461565).https://www.frontiersin.org/articles/10.3389/fphar.2025.1586332/fullEGFR mutantchemotherapytargeted therapyadvanced non small cell lung cancercombined therapy |
| spellingShingle | Siyan Peng Siyan Peng Zhixin Yu Zhixin Yu Honglin Zhu Honglin Zhu Chuwen Liang Chuwen Liang Huijuan Qiu Huijuan Qiu Shaodong Hong Shaodong Hong Yixin Zhou Yixin Zhou Comparative analysis of first-generation epidermal growth factor receptor inhibitors combined with chemotherapy versus third-generation epidermal growth factor receptor inhibitors in the treatment of advanced non-small cell lung cancer: a systematic review and meta-analysis Frontiers in Pharmacology EGFR mutant chemotherapy targeted therapy advanced non small cell lung cancer combined therapy |
| title | Comparative analysis of first-generation epidermal growth factor receptor inhibitors combined with chemotherapy versus third-generation epidermal growth factor receptor inhibitors in the treatment of advanced non-small cell lung cancer: a systematic review and meta-analysis |
| title_full | Comparative analysis of first-generation epidermal growth factor receptor inhibitors combined with chemotherapy versus third-generation epidermal growth factor receptor inhibitors in the treatment of advanced non-small cell lung cancer: a systematic review and meta-analysis |
| title_fullStr | Comparative analysis of first-generation epidermal growth factor receptor inhibitors combined with chemotherapy versus third-generation epidermal growth factor receptor inhibitors in the treatment of advanced non-small cell lung cancer: a systematic review and meta-analysis |
| title_full_unstemmed | Comparative analysis of first-generation epidermal growth factor receptor inhibitors combined with chemotherapy versus third-generation epidermal growth factor receptor inhibitors in the treatment of advanced non-small cell lung cancer: a systematic review and meta-analysis |
| title_short | Comparative analysis of first-generation epidermal growth factor receptor inhibitors combined with chemotherapy versus third-generation epidermal growth factor receptor inhibitors in the treatment of advanced non-small cell lung cancer: a systematic review and meta-analysis |
| title_sort | comparative analysis of first generation epidermal growth factor receptor inhibitors combined with chemotherapy versus third generation epidermal growth factor receptor inhibitors in the treatment of advanced non small cell lung cancer a systematic review and meta analysis |
| topic | EGFR mutant chemotherapy targeted therapy advanced non small cell lung cancer combined therapy |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2025.1586332/full |
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