{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T17:01:22Z","timestamp":1781629282581,"version":"3.54.5"},"reference-count":27,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T00:00:00Z","timestamp":1767744000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,2,4]],"date-time":"2026-02-04T00:00:00Z","timestamp":1770163200000},"content-version":"vor","delay-in-days":28,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Discov Onc"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To systematically evaluate the clinical efficacy, safety, and prognostic impact of third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), particularly osimertinib, in patients with advanced non-small cell lung cancer (NSCLC).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Method<\/jats:title>\n                    <jats:p>A comprehensive search of international and Chinese databases was conducted from inception to April 2025 to identify randomized controlled trials (RCTs) assessing osimertinib in advanced NSCLC. Data extraction and quality assessment were performed independently by two reviewers using the Cochrane Handbook (version 5.3). Meta-analysis was conducted using RevMan 5.4.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Result<\/jats:title>\n                    <jats:p>Nine RCTs involving 1,880 patients were included. Osimertinib significantly improved objective response rate (ORR) [OR\u2009=\u20092.99, 95% CI: 1.87\u20134.77] and disease control rate (DCR) [OR\u2009=\u20092.80, 95% CI: 1.38\u20135.67] compared to control therapies. The incidence of grade\u2009\u2265\u20093 adverse events was significantly lower in the osimertinib group [OR\u2009=\u20090.26, 95% CI: 0.14\u20130.47]. Osimertinib increased the risk of dermatologic events such as paronychia and rash but decreased gastrointestinal symptoms including nausea and vomiting.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Osimertinib is an effective and generally well-tolerated treatment option for patients with advanced NSCLC. While efficacy and safety are favorable, further research is needed to assess long-term outcomes and monitor serious adverse events.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s12672-025-04353-7","type":"journal-article","created":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T17:45:23Z","timestamp":1767807923000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Efficacy and safety of Osimertinib and other third-generation EGFR TKIs in advanced NSCLC: a systematic review and meta-analysis"],"prefix":"10.1007","volume":"17","author":[{"given":"Juan","family":"Lin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunxia","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinshan","family":"Weng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shanzuan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,1,7]]},"reference":[{"issue":"11","key":"4353_CR1","doi-asserted-by":"publisher","first-page":"1252","DOI":"10.1200\/JCO.23.01017","volume":"42","author":"T Mok","year":"2024","unstructured":"Mok T, et al. Nivolumab plus chemotherapy in epidermal growth factor receptor-Mutated metastatic Non-Small-Cell lung cancer after disease progression on epidermal growth factor receptor tyrosine kinase inhibitors: final results of checkmate 722. J Clin Oncol. 2024;42(11):1252\u201364.","journal-title":"J Clin Oncol"},{"issue":"13","key":"4353_CR2","doi-asserted-by":"publisher","first-page":"1888","DOI":"10.1111\/1759-7714.14272","volume":"13","author":"JW Chang","year":"2022","unstructured":"Chang JW, et al. Epidermal growth factor receptor tyrosine kinase inhibitors for de Novo T790M mutation: A retrospective study of 44 patients. Thorac Cancer. 2022;13(13):1888\u201397.","journal-title":"Thorac Cancer"},{"issue":"5","key":"4353_CR3","doi-asserted-by":"publisher","first-page":"687","DOI":"10.1007\/s11523-021-00839-w","volume":"16","author":"YN Lamb","year":"2021","unstructured":"Lamb YN. Osimertinib: A review in previously Untreated, EGFR Mutation-Positive, advanced NSCLC. Target Oncol. 2021;16(5):687\u201395.","journal-title":"Target Oncol"},{"issue":"18","key":"4353_CR4","doi-asserted-by":"publisher","first-page":"1711","DOI":"10.1056\/NEJMoa2027071","volume":"383","author":"YL Wu","year":"2020","unstructured":"Wu YL, et al. Osimertinib in resected EGFR-Mutated Non-Small-Cell lung cancer. N Engl J Med. 2020;383(18):1711\u201323.","journal-title":"N Engl J Med"},{"issue":"6","key":"4353_CR5","doi-asserted-by":"publisher","first-page":"925","DOI":"10.1007\/s11523-024-01094-5","volume":"19","author":"M Hibino","year":"2024","unstructured":"Hibino M, et al. Impact of First-Line osimertinib and other EGFR-Tyrosine kinase inhibitors on overall survival in untreated advanced EGFR-Mutated Non-small cell lung cancer in japan: updated data from TREAD project 01. Target Oncol. 2024;19(6):925\u201339.","journal-title":"Target Oncol"},{"issue":"4","key":"4353_CR6","doi-asserted-by":"publisher","first-page":"328","DOI":"10.1200\/JCO.20.01171","volume":"39","author":"MS Ewer","year":"2021","unstructured":"Ewer MS, et al. Cardiac safety of osimertinib: A review of data. J Clin Oncol. 2021;39(4):328\u201337.","journal-title":"J Clin Oncol"},{"issue":"1","key":"4353_CR7","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1007\/s13691-020-00450-2","volume":"10","author":"S Ikebe","year":"2021","unstructured":"Ikebe S, et al. Osimertinib-induced cardiac failure with QT prolongation and torsade de pointes in a patient with advanced pulmonary adenocarcinoma. Int Cancer Conf J. 2021;10(1):68\u201371.","journal-title":"Int Cancer Conf J"},{"issue":"6","key":"4353_CR8","doi-asserted-by":"publisher","first-page":"823","DOI":"10.2169\/internalmedicine.3689-19","volume":"59","author":"J Itano","year":"2020","unstructured":"Itano J, et al. Successful Re-administration of osimertinib in osimertinib-induced interstitial lung disease with an organizing pneumonia pattern: A case report and literature review. Intern Med. 2020;59(6):823\u20138.","journal-title":"Intern Med"},{"issue":"1","key":"4353_CR9","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1186\/s13045-022-01391-4","volume":"15","author":"K Fu","year":"2022","unstructured":"Fu K, et al. Therapeutic strategies for EGFR-mutated non-small cell lung cancer patients with osimertinib resistance. J Hematol Oncol. 2022;15(1):173.","journal-title":"J Hematol Oncol"},{"key":"4353_CR10","doi-asserted-by":"crossref","unstructured":"Bertoli E et al. Acquired resistance to osimertinib in EGFR-Mutated Non-Small cell lung cancer: how do we overcome it? Int J Mol Sci, 2022. 23(13).","DOI":"10.3390\/ijms23136936"},{"issue":"7","key":"4353_CR11","doi-asserted-by":"publisher","first-page":"629","DOI":"10.1056\/NEJMoa1612674","volume":"376","author":"TS Mok","year":"2017","unstructured":"Mok TS, et al. Osimertinib or Platinum-Pemetrexed in EGFR T790M-Positive lung cancer. N Engl J Med. 2017;376(7):629\u201340.","journal-title":"N Engl J Med"},{"issue":"2","key":"4353_CR12","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1056\/NEJMoa1713137","volume":"378","author":"JC Soria","year":"2018","unstructured":"Soria JC, et al. Osimertinib in untreated EGFR-Mutated advanced Non-Small-Cell lung cancer. N Engl J Med. 2018;378(2):113\u201325.","journal-title":"N Engl J Med"},{"key":"4353_CR13","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1016\/j.lungcan.2018.04.012","volume":"121","author":"K Nie","year":"2018","unstructured":"Nie K, et al. Osimertinib compared docetaxel-bevacizumab as third-line treatment in EGFR T790M mutated non-small-cell lung cancer. Lung Cancer. 2018;121:5\u201311.","journal-title":"Lung Cancer"},{"issue":"04","key":"4353_CR14","first-page":"395","volume":"33","author":"Y Lixiang","year":"2019","unstructured":"Lixiang Y, Ethan SH, et al. Efficacy analysis of oxitinib in the treatment of patients with advanced T790M mutant lung adenocarcinoma. J Chin Practical Diagnosis Therapy. 2019;33(04):395\u20137.","journal-title":"J Chin Practical Diagnosis Therapy"},{"issue":"24","key":"4353_CR15","first-page":"2952","volume":"17","author":"XY Liu Dan","year":"2019","unstructured":"Liu Dan XY, Chen, Guoqing, et al. Efficacy and prognosis analysis of oxitinib in the treatment of advanced non-small cell lung cancer patients with T7900M mutation positive. Oncol Progress. 2019;17(24):2952\u20135.","journal-title":"Oncol Progress"},{"issue":"07","key":"4353_CR16","first-page":"1257","volume":"24","author":"ZZ Wang Rukun","year":"2019","unstructured":"Wang Rukun ZZ, Bin Q, et al. Clinical efficacy of oxitinib in the treatment of EGFR T790M positive non-small cell lung cancer. J Clin Pulmonary Med. 2019;24(07):1257\u201360.","journal-title":"J Clin Pulmonary Med"},{"key":"4353_CR17","unstructured":"Dai Weijing LH. Dai Danjing., Therapeutic effect of oxitinib on NSCLC patients with EGFR T790M mutation and its influence on the level of miR-21. International Journal of Laboratory Medicine, 2020. 41(14): pp. 1772\u20131775."},{"issue":"04","key":"4353_CR18","first-page":"433","volume":"36","author":"W Peng","year":"2024","unstructured":"Peng W, Li XFY, et al. Clinical observation of oxitinib combined with chemotherapy in the treatment of advanced non-small cell lung cancer. J Henan Med Coll. 2024;36(04):433\u20137.","journal-title":"J Henan Med Coll"},{"issue":"04","key":"4353_CR19","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1186\/s13020-025-01075-4","volume":"22","author":"F Yuyan","year":"2025","unstructured":"Yuyan. F. Efficacy and safety analysis of oxitinib combined with pemetrexed and cisplatin as First-line regimen in the treatment of advanced Non-small cell lung cancer. Med Innov China. 2025;22(04):40\u20134.","journal-title":"Med Innov China"},{"issue":"10","key":"4353_CR20","doi-asserted-by":"publisher","first-page":"1830","DOI":"10.1200\/JCO.22.02186","volume":"41","author":"RS Herbst","year":"2023","unstructured":"Herbst RS, et al. Adjuvant osimertinib for resected EGFR-Mutated stage IB-IIIA Non-Small-Cell lung cancer: updated results from the phase III randomized ADAURA trial. J Clin Oncol. 2023;41(10):1830\u201340.","journal-title":"J Clin Oncol"},{"issue":"1","key":"4353_CR21","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1186\/s12943-022-01547-3","volume":"21","author":"Z Pan","year":"2022","unstructured":"Pan Z, et al. Cholesterol promotes EGFR-TKIs resistance in NSCLC by inducing EGFR\/Src\/Erk\/SP1 signaling-mediated erralpha re-expression. Mol Cancer. 2022;21(1):77.","journal-title":"Mol Cancer"},{"key":"4353_CR22","doi-asserted-by":"publisher","first-page":"100987","DOI":"10.1016\/j.drup.2023.100987","volume":"70","author":"WJ Liu","year":"2023","unstructured":"Liu WJ, et al. Elevated NOX4 promotes tumorigenesis and acquired EGFR-TKIs resistance via enhancing IL-8\/PD-L1 signaling in NSCLC. Drug Resist Updat. 2023;70:100987.","journal-title":"Drug Resist Updat"},{"issue":"2","key":"4353_CR23","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1007\/s11523-021-00794-6","volume":"16","author":"Y Cheng","year":"2021","unstructured":"Cheng Y, et al. Osimertinib versus comparator EGFR TKI as First-Line treatment for EGFR-Mutated advanced NSCLC: FLAURA China, A randomized study. Target Oncol. 2021;16(2):165\u201376.","journal-title":"Target Oncol"},{"issue":"5","key":"4353_CR24","doi-asserted-by":"publisher","first-page":"497","DOI":"10.6004\/jnccn.2022.0025","volume":"20","author":"DS Ettinger","year":"2022","unstructured":"Ettinger DS, et al. Non-Small cell lung Cancer, version 3.2022, NCCN clinical practice guidelines in oncology. J Natl Compr Canc Netw. 2022;20(5):497\u2013530.","journal-title":"J Natl Compr Canc Netw"},{"issue":"5","key":"4353_CR25","doi-asserted-by":"publisher","first-page":"749","DOI":"10.2169\/internalmedicine.3932-24","volume":"64","author":"S Fujimoto","year":"2025","unstructured":"Fujimoto S, et al. Successful treatment with ramucirumab plus erlotinib following Osimertinib-induced interstitial lung disease. Intern Med. 2025;64(5):749\u201351.","journal-title":"Intern Med"},{"key":"4353_CR26","doi-asserted-by":"publisher","first-page":"655808","DOI":"10.3389\/fcvm.2021.655808","volume":"8","author":"M Kondo","year":"2021","unstructured":"Kondo M, et al. Case report: QT prolongation and abortive sudden death observed in an 85-Year-Old female patient with advanced lung cancer treated with tyrosine kinase inhibitor osimertinib. Front Cardiovasc Med. 2021;8:655808.","journal-title":"Front Cardiovasc Med"},{"issue":"8","key":"4353_CR27","doi-asserted-by":"publisher","first-page":"1007","DOI":"10.1080\/14740338.2023.2294924","volume":"23","author":"JY Byun","year":"2024","unstructured":"Byun JY, et al. Long QT syndrome after using EGFR-TKIs in older patients with advanced non-small cell lung cancer. Expert Opin Drug Saf. 2024;23(8):1007\u201315.","journal-title":"Expert Opin Drug Saf"}],"container-title":["Discover Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s12672-025-04353-7","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12672-025-04353-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12672-025-04353-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T16:16:10Z","timestamp":1781626570000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s12672-025-04353-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,7]]},"references-count":27,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["4353"],"URL":"https:\/\/doi.org\/10.1007\/s12672-025-04353-7","relation":{},"ISSN":["2730-6011"],"issn-type":[{"value":"2730-6011","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,7]]},"assertion":[{"value":"27 July 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 December 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 January 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not Applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not Applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"232"}}