EGFR mutations and clinical outcomes of chemotherapy for advanced non-small cell lung cancer: a meta-analysis
Abstract
Background This meta-analysis was performed to assess whether epidermal growth factor receptor (EGFR) mutation status was associated with objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) in patients with advanced non-small cell lung cancer (NSCLC) treated with chemotherapy.Method We systematically identified eligible articles investigating the effects of chemotherapy in patients with NSCLC stratified by EGFR mutation status. The summary risk ratio (RR) for ORR and hazard ratios (HRs) for both PFS and OS were calculated using the inverse variance formula of meta-analysis.Results Identification for the current meta-analysis: 5 prospective studies (n=875) and 18 retrospective studies (n=1934) for ORR; 2 prospective studies (n=434) and 10 retrospective studies (n=947) for PFS; 2 prospective studies (n=438) and 7 retrospective studies (n=711) for OS. The ORR was significantly higher in patients with EGFR mutations in prospective studies (RR=1.42; 95% confidence interval [CI], 1.16-1.74; P=0.001), but not in retrospective studies (RR=1.12; 95% CI, 0.96-1.32; P=0.146). There was no obvious association between EGFR mutations and PFS both in prospective (HR=0.84; 95% CI: 0.65-1.09; P=0.197) and retrospective (HR=1.02; 95% CI: 0.87-1.18; P=0.838) studies. Association between EGFR mutations and OS was also not seen in prospective studies (HR=0.74; 95% CI: 0.27-2.05; P=0.566), but was seen in retrospective studies (HR=0.48; 95% CI: 0.33-0.72; P<0.001; I(2)=75.9%; P<0.001) with significant heterogeneity.Conclusion EGFR mutations in advanced NSCLC may be associated with higher ORRs to chemotherapy, but may have nothing to do with PFS and OS. Further prospective studies are required to identify the influence of EGFR mutations on chemotherapy effects in advanced NSCLC.
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Patients with EGFR mutations usually exhibit increased ORR to first-line chemotherapy.
“A direct observation of increased sensitivity to chemotherapy is the fact that patients with EGFR mutations usually exhibit increased ORR to first-line chemotherapy [47].”
From A decade of EGFR inhibition in EGFR-mutated non small cell lung cancer (NSCLC): Old successes and future perspectives (2015) · cites this paper as [47]
Cites
(2014) · Medical Entomology and Zoology · Cited by 17,633 · see citing works
Gefitinib or Carboplatin–Paclitaxel in Pulmonary Adenocarcinoma
Mok, T. S., Wu, Y.-L., Thongprasert, S., Yang, C.-H., Chu, D.-T., Saijo, N., Sunpaweravong, P., Han, B., Margono, B., Ichinose, Y., et al. (2009) · New England Journal of Medicine · doi:10.1056/nejmoa0810699 · Cited by 8,261 · see citing works
Practical methods for incorporating summary time-to-event data into meta-analysis.
Tierney, J. F., Stewart, L. A., Ghersi, D., Burdett, S., & Sydes, M. R. (2007) · Trials · doi:10.1186/1745-6215-8-16 · Cited by 6,208 · see citing works
Gefitinib-Sensitizing EGFR Mutations in Lung Cancer Activate Anti-Apoptotic Pathways
Sordella, R., Bell, D. W., Haber, D. A., & Settleman, J. E. (2004) · Science · doi:10.1126/science.1101637 · Cited by 1,605 · see citing works
Eberhard, D. A., Johnson, B. E., Amler, L. C., Goddard, A. D., Heldens, S., Herbst, R. S., Ince, W. L., Janne, P. A., Januario, T., Johnson, D. H., et al. (2005) · Journal of Clinical Oncology · doi:10.1200/jco.2005.02.857 · Cited by 1,453 · see citing works
Bell, D. W., Lynch, T. J., Haserlat, S. M., Harris, P. L., Okimoto, R. A., Brannigan, B. W., Sgroi, D. C., Muir, B., Riemenschneider, M. J., Iacona, R. B., et al. (2005) · Journal of Clinical Oncology · doi:10.1200/jco.2005.02.7078 · Cited by 598 · see citing works
Douillard, J.-Y., Shepherd, F. A., Hirsh, V., Mok, T., Socinski, M. A., Gervais, R., Liao, M.-L., Bischoff, H., Reck, M., Sellers, M. V., et al. (2010) · Journal of Clinical Oncology · doi:10.1200/jco.2009.24.3030 · Cited by 492 · see citing works
Khambata‐Ford, S., Harbison, C. T., Hart, L. L., Awad, M., Xu, L., Horak, C. E., Dakhil, S. R., Hermann, R. C., Lynch, T. J., & Weber, M. R. (2010) · Journal of Clinical Oncology · doi:10.1200/jco.2009.25.2890 · Cited by 265 · see citing works
Camidge, D. R., Kono, S. A., Lu, X. J. D., Okuyama, S., Barón, A. E., Oton, A. B., Davies, A. M., Varella‐Garcia, M., Franklin, W. A., & Doebele, R. C. (2011) · Journal of Thoracic Oncology · doi:10.1097/jto.0b013e31820cf053 · Cited by 238 · see citing works
Yang, C.-H., Yu, C., Shih, J., Chang, Y., Hu, F., Tsai, M.-C., Chen, K., Lin, Z., Huang, C.-J., Shun, C., et al. (2008) · Journal of Clinical Oncology · doi:10.1200/jco.2007.15.6695 · Cited by 235 · see citing works
Millett, G. A. (2008) · JAMA · doi:10.1001/jama.300.14.1674 · Cited by 223 · see citing works
Schoenleber, S. J., Kurtz, D. M., Talwalkar, J. A., Roberts, L. R., & Gores, G. J. (2009) · British Journal of Cancer · doi:10.1038/sj.bjc.6605017 · Cited by 207 · see citing works
Bai, H., Wang, Z., Chen, K., Zhao, J., Lee, J. J., Wang, S., Zhou, Q., Zhuo, M., Mao, L., An, T., et al. (2012) · Journal of Clinical Oncology · doi:10.1200/jco.2011.39.3744 · Cited by 199 · see citing works
Lee, J., Kim, T. M., Lee, S., Kim, D., Kim, S., Jeon, Y., Chung, D. H., Kim, W. H., Kim, Y. T., Yang, S.-C., et al. (2011) · Journal of Thoracic Oncology · doi:10.1097/jto.0b013e3182208fc2 · Cited by 159 · see citing works
Dahabreh, I. J., Linardou, H., Siannis, F., Kosmidis, P., Bafaloukos, D. I., & Murray, S. J. (2009) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-09-1660 · Cited by 137 · see citing works
Gao, G., Ren, S., Li, A., Xu, J., Xu, Q., Su, C., Guo, J., Deng, Q., & Zhou, C. (2011) · International Journal of Cancer · doi:10.1002/ijc.27396 · Cited by 133 · see citing works
Kalikaki, A., Koutsopoulos, A. V., Hatzidaki, D., Trypaki, M., Kontopodis, E., Stathopoulos, E. N., Mavroudis, D., Georgoulias, V., & Voutsina, A. (2009) · Lung Cancer · doi:10.1016/j.lungcan.2009.09.010 · Cited by 91 · see citing works
Cappuzzo, F., Ligorio, C., Toschi, L., Rossi, E., Trisolini, R., Paioli, D., Magrini, E., Finocchiaro, G., Bartolini, S., Cancellieri, A., et al. (2007) · Journal of Thoracic Oncology · doi:10.1097/01.jto.0000268676.79872.9b · Cited by 89 · see citing works
Guan, J.-L., Zhong, W.-Z., An, S.-J., Yang, J.-J., Su, J., Chen, Z.-H., Yan, H.-H., Chen, Z.-Y., Huang, Z.-M., Zhang, X.-C., et al. (2013) · Annals of Surgical Oncology · doi:10.1245/s10434-012-2754-z · Cited by 87 · see citing works
Chen, S., Zhang, J., Wang, R., Luo, X., & Chen, H. (2010) · Lung Cancer · doi:10.1016/j.lungcan.2010.05.010 · Cited by 84 · see citing works
Gong, W., Zhang, X., Wu, J., Chen, L., Li, L., Sun, J., Lv, Y., Wei, X., Du, Y., Jin, H., et al. (2011) · Lung Cancer · doi:10.1016/j.lungcan.2011.08.003 · Cited by 79 · see citing works
Hotta, K., Kiura, K., Toyooka, S., Takigawa, N., Soh, J., Fujiwara, Y., Tabata, M., Date, H., & Tanimoto, M. (2007) · Journal of Thoracic Oncology · doi:10.1097/jto.0b013e318074bc0d · Cited by 67 · see citing works
Second‐line treatments after first‐line gefitinib therapy in advanced nonsmall cell lung cancer
Wu, J., Shih, J., Yang, C., Chen, K., Ho, C., Yu, C., & Yang, P. (2009) · International Journal of Cancer · doi:10.1002/ijc.24657 · Cited by 58 · see citing works
Lee, J. K., Park, H. S., Kim, D., Kulig, K., Kim, T. M., Lee, S., Jeon, Y., Chung, D. H., Heo, D. S., Kim, W., et al. (2011) · Cancer · doi:10.1002/cncr.26668 · Cited by 52 · see citing works
Wu, M., Zhao, J., Song, S. W., Zhuo, M., Wang, X., Bai, H., Wang, S., Yang, L., An, T., Zhang, Y., et al. (2009) · Lung Cancer · doi:10.1016/j.lungcan.2009.04.011 · Cited by 51 · see citing works
Bakker, E. (2006) · Clinical Chemistry · doi:10.1373/clinchem.2005.066068 · Cited by 48 · see citing works
Wu, S., Yang, C.-H., Yu, C., Lee, J., Hsu, Y.-C., Chang, Y., Shih, J., & Yang, P. (2010) · Lung Cancer · doi:10.1016/j.lungcan.2010.10.012 · Cited by 42 · see citing works
Okamoto, I., Aoe, K., Kato, T., Hosomi, Y., Yokoyama, A., Imamura, F., Kiura, K., Hirashima, T., Nishio, M., Nogami, N., et al. (2013) · Investigational New Drugs · doi:10.1007/s10637-013-9941-z · Cited by 41 · see citing works
Campos-Parra, A. D., Zuloaga, C., Manríquez, M. E. V., Avilés, A., Borbolla-Escoboza, J. R., Cardona, A. F., Meneses, A., & Arrieta, O. G. (2013) · American Journal of Clinical Oncology · doi:10.1097/coc.0b013e318287bb23 · Cited by 41 · see citing works
Lee, K.-H., Han, S., Hwang, P. G., Oh, D., Kim, D., Chung, D. H., Im, S., Kim, T., Heo, D. S., & Bang, Y. (2006) · Japanese Journal of Clinical Oncology · doi:10.1093/jjco/hyl039 · Cited by 29 · see citing works
Lin, C., Hsu, H.-H., Shun, C., Shih, J., Lin, Z., Yu, C., Chen, G. G., Hsin, M. K. Y., Lam, K. C., Leung, L. K. S., et al. (2010) · Journal of Thoracic Oncology · doi:10.1097/jto.0b013e3181e9db73 · Cited by 28 · see citing works
EGFR mutations as a predictive marker of cytotoxic chemotherapy
Park, J. H., Lee, S., Keam, B., Kim, T. M., Kim, D., Yang, S.-C., Kim, Y. W., & Heo, D. S. (2012) · Lung Cancer · doi:10.1016/j.lungcan.2012.03.020 · Cited by 25 · see citing works
Qin, L., Zhong, W., Zhang, L., Li, L., & Wang, M. (2011) · PubMed · Cited by 24 · see citing works
Millett, G. A., Flores, S. A., Marks, G. N., Reed, J. B., & Herbst, J. H. (2017) · Cited by 22 · see citing works
Dong, X., Zhao, X., Hao, Y., Wei, Y., Qiuwei, Y., & Du, J. (2013) · Clinical Lung Cancer · doi:10.1016/j.cllc.2013.05.004 · Cited by 21 · see citing works
Han, Y., Wang, X., Xiao, N., & Liu, Z. (2013) · Asian Pacific Journal of Cancer Prevention · doi:10.7314/apjcp.2013.14.5.2987 · Cited by 18 · see citing works
Epidermal Growth Factor Receptor Mutations Are Associated with Docetaxel Sensitivity in Lung Cancer
Yoshimasu, T., Oura, S., Ohta, F., Hirai, Y., 内藤, 古., Nakamura, R., Nishiguchi, H., Hashimoto, S., Kawago, M., & Okamura, Y. (2011) · Journal of Thoracic Oncology · doi:10.1097/jto.0b013e318221f71a · Cited by 15 · see citing works
Yoshida, K., Yatabe, Y., Jangchul, P., Ogawa, S., Park, J. Y., Shimizu, J., Horio, Y., Matsuo, K., Mitsudomi, T., & Hida, T. (2009) · Journal of Cancer Research and Clinical Oncology · doi:10.1007/s00432-009-0685-2 · Cited by 13 · see citing works
Li, F., Bai, H., Li, X., Wu, M., Yu, R., Shi, A., Li, Y., Wang, J., & Zhu, G. (2011) · Europe PMC (PubMed Central) · doi:10.3779/j.issn.1009-3419.2011.09.03 · Cited by 11 · see citing works
Zhuo, M., Wu, M., Zhao, J., Song, S. W., Bai, H., Wang, S., Yang, L., An, T., Wang, X., Duan, J., et al. (2011) · PubMed · Cited by 7 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Russo, A., Franchina, T., Rita Ricciardi, G. R., Picone, A., Ferraro, G., Zanghì, M., Toscano, G., Giordano, A., & Adamo, V. (2015) · Oncotarget · doi:10.18632/oncotarget.4254 · Cited by 173 · see citing works
Molecular histology of lung cancer: From targets to treatments
Wood, S. L., Pernemalm, M., Crosbie, P. A. J., & Whetton, A. D. (2015) · Cancer Treatment Reviews · doi:10.1016/j.ctrv.2015.02.008 · Cited by 161 · see citing works
Kovačević, Ž., Menezes, S. V., Sahni, S., Kalinowski, D. S., Bae, D.-H., Lane, D. J. R., & Richardson, D. R. (2015) · Journal of Biological Chemistry · doi:10.1074/jbc.m115.689653 · Cited by 82 · see citing works
Zarogoulidis, P., Petanidis, S., Kioseoglou, E., Domvri, K., Anestakis, D., & Zarogoulidis, P. (2015) · Cellular Signalling · doi:10.1016/j.cellsig.2015.04.009 · Cited by 72 · see citing works
Togashi, Y., Hayashi, H., Okamoto, K., Fumita, S., Terashima, M., Velasco, M. A. D., Sakai, K., Fujita, Y., Tomida, S., Nakagawa, K., et al. (2015) · Lung Cancer · doi:10.1016/j.lungcan.2015.01.027 · Cited by 36 · see citing works
Lin, C., Wu, Y.-M., Hsieh, M., Wang, C., Wu, C.-Y., Chen, Y.-J., & Fang, Y. (2017) · PLoS ONE · doi:10.1371/journal.pone.0186567 · Cited by 21 · see citing works
Advanced non small cell lung cancer: response to microwave ablation and EGFR Status
Wei, Z., Ye, X., Yang, X., Huang, G., Li, W., Wang, J., Han, X., Meng, M., & Ni, Y. (2016) · European Radiology · doi:10.1007/s00330-016-4474-4 · Cited by 18 · see citing works
Wang, Z., Yang, H., Luo, S., Liu, B., Zhang, N., Li, L., Zhou, S., Shen, R., & Xie, X. (2017) · Lung Cancer · doi:10.1016/j.lungcan.2017.07.029 · Cited by 17 · see citing works
Rotella, V., Fornaro, L., Vasile, E., Tibaldi, C., Boldrini, L., Chella, A., D’Incecco, A., Cirigliano, G., Chioni, A., Lupi, C., et al. (2014) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/preaccept-1417843480141843 · Cited by 13 · see citing works
Li, C., Liu, W., Ning, J.-F., Meng, W.-Q., Hu, J., Zhao, Y., & Liu, C. (2015) · Drug Design Development and Therapy · doi:10.2147/dddt.s85357 · Cited by 12 · see citing works
Zhang, H., Zhan, C., Ke, J., Xue, Z., Zhang, A., Xu, K., Shen, Z., Yu, L., & Chen, L. (2015) · Oncotarget · doi:10.18632/oncotarget.6491 · Cited by 11 · see citing works
RNA-Seq and Network Analysis Revealed Interacting Pathways in TGF-β-Treated Lung Cancer Cell Lines
Li, Y., Rouhi, O., Chen, H., Ramirez, R., Borgia, J. A., & Deng, Y. (2014) · Cancer Informatics · doi:10.4137/cin.s14073 · Cited by 8 · see citing works
Zheng, S., Wang, R., Zhang, Y., Pan, Y., Cheng, C., Zheng, D., Sun, Y., & Chen, H. (2016) · Cancer Medicine · doi:10.1002/cam4.764 · Cited by 7 · see citing works
Yan, X., Inta, A., Yang, X., Pandith, H., Disayathanoowat, T., & Yang, L. (2024) · Pharmaceuticals · doi:10.3390/ph17111429 · Cited by 6 · see citing works
Jiang, J., Wang, C., Yu, X., Sheng, D., Chen, Z., Ren, M., Wu, Y., Shen, J., Jin, M., & Xu, S. (2015) · Experimental and Molecular Pathology · doi:10.1016/j.yexmp.2015.10.002 · Cited by 5 · see citing works
Erdoğan, B., Kodaz, H., Karabulut, S., Cinkaya, A., Tozkır, H., Tanrıverdi, Ö., Çabuk, D., Hacıoğlu, M. B., Türkmen, E., Hacıbekiroğlu, İ., et al. (2016) · Bosnian Journal of Basic Medical Sciences · doi:10.17305/bjbms.2016.1380 · Cited by 5 · see citing works
Zhan, S., Lu, X., Guo, H., Liu, Y., Li, Z., Xu, W., Xia, F., Tang, H., Tian, Y., Chen, J., et al. (2025) · Journal of Hepatocellular Carcinoma · doi:10.2147/jhc.s527095 · Cited by 3 · see citing works
Zhang, N., Xu, D., Liu, B., Shi, X., Xie, X., & Wang, Z. (2022) · International Immunopharmacology · doi:10.1016/j.intimp.2022.109299 · Cited by 2 · see citing works
Qin, N., Zhang, Q., Wang, J., Zhang, H., Gu, Y., Yang, X., Li, X., Lv, J., Wu, Y., Nong, J., et al. (2015) · Europe PMC (PubMed Central) · doi:10.3779/j.issn.1009-3419.2015.03.02 · Cited by 2 · see citing works
Self-citationSuda, K., Fujino, K., Yoshikawa, M., Shien, K., Suzawa, K., Nomura, K., Fukuda, S., Ohara, S., Hamada, A., Kinoshita, F., et al. (2025) · European Journal of Cardio-Thoracic Surgery · doi:10.1093/ejcts/ezaf239 · Cited by 1 · see citing works
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Nursal, A. F. (2015) · Dicle Medical Journal / Dicle Tip Dergisi · doi:10.5798/diclemedj.0921.2015.01.0545
Chen, L., Qi, Q., Zhu, M., Zhang, Y., Peng, Y., & Liu, Y. (2022) · Biomedical Reports · doi:10.3892/br.2022.1539
Takamori, S., Shimokawa, T., Osoegawa, A., Abe, M., Takumi, Y., Sugawara, S., Niho, S., Goto, Y., Okamoto, H., Hotta, K., et al. (2025) · JTO Clinical and Research Reports · doi:10.1016/j.jtocrr.2025.100897
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Abdelmaksoud‐Dammak, R., Ammous-Boukhris, N., Charfi, S., Kallel, N., Khemakhem, R., Feki, A., Boudawara, T. S., Yangui, I., Khanfir, A., & Mokdad‐Gargouri, R. (2026) · Molecular Biology Reports · doi:10.1007/s11033-026-11472-z
- Authors
- Zhang, Q., Dai, H.-H., Dong, H.-Y., Sun, C.-T., Yang, Z., & Han, J.-Q.
- Affiliations
- Shandong University (CN)
- Corresponding author
- Yang, Zhe
- Venue
- Lung Cancer
- Publisher
- Elsevier BV
- Published
- 2014-09
- Volume
- 85
- Issue
- 3
- Pages
- 339-345
- ISSN
- 0169-5002 (ISSN-L)
- OpenAlex
- W2057942347
- Cited by
- 25
- References
- 40
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 1 · 2022: 2 · 2017: 2 · 2016: 3 · 2015: 11 · 2014: 2
- FWCI
- 1.03
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Lung Cancer (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Diagnosis and Treatment
- Health Sciences › Medicine › Oncology › Lung Cancer Research Studies
- Keywords
- EGFR mutation, non-small cell lung cancer, advanced non-small cell lung cancer, chemotherapy response, objective response rate, progression-free survival, overall survival, predictive biomarkers, EGFR tyrosine kinase inhibitors, EGFR inhibitor resistance
- MeSH terms
- Antineoplastic Combined Chemotherapy Protocols, Carcinoma, Non-Small-Cell Lung, Humans, Lung Neoplasms, Mutation, Neoplasm Staging, Odds Ratio, Treatment Outcome, Publication Bias, ErbB Receptors
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