{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T12:54:15Z","timestamp":1793192055301,"version":"4.5.0"},"reference-count":25,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"10","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["JCO Oncol Pract"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:sec>\n                    <jats:title>PURPOSE<\/jats:title>\n                    <jats:p>Although clinical trials support osimertinib's efficacy over standard epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in metastatic EGFR-mutant non\u2013small cell lung cancer (NSCLC), large real-world comparisons against first-generation TKIs are limited. We compared the real-world effectiveness and safety of first-line osimertinib versus first-generation TKIs (erlotinib, gefitinib) using a target trial emulation approach.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>This retrospective cohort study used the TriNetX Research Network global database. We identified adults with newly diagnosed metastatic EGFR-mutant NSCLC initiating first-line EGFR-TKI therapy (January 2014-March 2025). After 1:1 propensity score matching (PSM), overall survival (OS; primary outcome) and safety were compared between treatment arms.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      Following PSM, a total of 3,168 patients (1,584 per arm) were analyzed. The median OS was significantly longer with osimertinib compared with first-generation TKIs (1,505\n                      <jats:italic toggle=\"yes\">v<\/jats:italic>\n                      901 days; hazard ratio [HR], 0.612 [95% CI, 0.549 to 0.683];\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt; .001). Survival benefits were consistent across subgroups, particularly pronounced in Asian patients (HR, 0.439). First-generation TKIs had higher rates of dermatologic toxicities, severe infections, and hospitalizations. Osimertinib showed higher rates of abnormal ECG findings and thrombocytopenia. Sensitivity analyses confirmed the robustness of the primary findings.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>In this large real-world comparative effectiveness study using target trial emulation, first-line osimertinib was associated with substantially prolonged OS and a favorable safety profile, including lower rates of severe infections and hospitalizations, compared with first-generation EGFR-TKIs in patients with metastatic EGFR-mutant NSCLC.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1200\/op-25-00788","type":"journal-article","created":{"date-parts":[[2025,12,9]],"date-time":"2025-12-09T20:59:40Z","timestamp":1765313980000},"page":"1844-1853","update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":1,"title":["Osimertinib Versus First-Generation Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors for Metastatic EGFR-Mutant Non\u2013Small Cell Lung Cancer: A Target Trial Emulation Study of Real-World Survival and Safety Outcomes"],"prefix":"10.1200","volume":"22","author":[{"given":"Ren-Hua","family":"Ye","sequence":"first","affiliation":[{"name":"Division of Hematology and Oncology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical University, Taipei, Taiwan"},{"name":"Department of Oncology, Tri-Service General Hospital, National Defense Medical University, Taipei, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3304-4643","authenticated-orcid":true,"given":"Hong-Jie","family":"Jhou","sequence":"additional","affiliation":[{"name":"Neurological Institute, Changhua Christian Hospital, Changhua, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hsin-Yu","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Family Medicine, Chi Mei Medical Center, Tainan, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0692-7408","authenticated-orcid":true,"given":"Li-Ting","family":"Kao","sequence":"additional","affiliation":[{"name":"Graduate Institute of Life Sciences, National Defense Medical University, Taipei, Taiwan"},{"name":"School of Pharmacy, National Defense Medical University, Taipei, Taiwan"},{"name":"Department of Pharmacy Practice, Tri-Service General Hospital, Taipei, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6296-0689","authenticated-orcid":true,"given":"Tina Yi-Jin","family":"Hsieh","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Beth Israel Deaconess Medical Center, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9170-7439","authenticated-orcid":true,"given":"Yu-Han","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Englewood Hospital and Medical Center, Englewood, NJ"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyi","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, NYC Health + Hospitals\/Jacobi, Albert Einstein College of Medicine, Bronx, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3953-5243","authenticated-orcid":true,"given":"Ming-Shen","family":"Dai","sequence":"additional","affiliation":[{"name":"Division of Hematology and Oncology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical University, Taipei, Taiwan"},{"name":"Department of Oncology, Tri-Service General Hospital, National Defense Medical University, Taipei, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8378-1687","authenticated-orcid":true,"given":"Ching-Liang","family":"Ho","sequence":"additional","affiliation":[{"name":"Division of Hematology and Oncology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical University, Taipei, Taiwan"},{"name":"Department of Oncology, Tri-Service General Hospital, National Defense Medical University, Taipei, Taiwan"},{"name":"Division of Hematology and Oncology, Medical Department, Taipei Tzu Chi Hospital, Taipei, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0280-6417","authenticated-orcid":true,"given":"Po-Huang","family":"Chen","sequence":"additional","affiliation":[{"name":"Division of Hematology and Oncology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical University, Taipei, Taiwan"},{"name":"Department of Oncology, Tri-Service General Hospital, National Defense Medical University, Taipei, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6061-5168","authenticated-orcid":true,"given":"Cho-Hao","family":"Lee","sequence":"additional","affiliation":[{"name":"Division of Hematology and Oncology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical University, Taipei, Taiwan"},{"name":"Department of Oncology, Tri-Service General Hospital, National Defense Medical University, Taipei, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"233","reference":[{"key":"e_1_3_7_2_2","first-page":"2892","article-title":"EGFR mutation incidence in non-small-cell lung cancer of adenocarcinoma histology: A systematic review and global map by ethnicity (mutMapII)","volume":"5","author":"Midha A","year":"2015","unstructured":"Midha A, Dearden S, McCormack R: EGFR mutation incidence in non-small-cell lung cancer of adenocarcinoma histology: A systematic review and global map by ethnicity (mutMapII). Am J Cancer Res 5:2892-2911, 2015","journal-title":"Am J Cancer Res"},{"key":"e_1_3_7_3_2","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.12587"},{"key":"e_1_3_7_4_2","doi-asserted-by":"publisher","DOI":"10.1097\/JTO.0000000000000422"},{"key":"e_1_3_7_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjc.6604373"},{"key":"e_1_3_7_6_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0810699"},{"key":"e_1_3_7_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(16)30033-X"},{"key":"e_1_3_7_8_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2016.70.3223"},{"key":"e_1_3_7_9_2","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-14-0337"},{"key":"e_1_3_7_10_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1713137"},{"key":"e_1_3_7_11_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2018.77.9363"},{"key":"e_1_3_7_12_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.23.02219"},{"key":"e_1_3_7_13_2","doi-asserted-by":"crossref","first-page":"e0212831","DOI":"10.1371\/journal.pone.0212831","article-title":"Correction: Real-world management of patients with epidermal growth factor receptor (EGFR) mutation-positive non-small-cell lung cancer in the USA","volume":"14","author":"Li Y","year":"2019","unstructured":"Li Y, Appius A, Pattipaka T, et al: Correction: Real-world management of patients with epidermal growth factor receptor (EGFR) mutation-positive non-small-cell lung cancer in the USA. PLoS One 14:e0212831, 2019","journal-title":"PLoS One"},{"key":"e_1_3_7_14_2","doi-asserted-by":"publisher","DOI":"10.2217\/fon-2020-0740"},{"key":"e_1_3_7_15_2","doi-asserted-by":"publisher","DOI":"10.1093\/aje\/kwv254"},{"key":"e_1_3_7_16_2","doi-asserted-by":"crossref","first-page":"e071108","DOI":"10.1136\/bmj-2022-071108","article-title":"Target trial emulation: Applying principles of randomised trials to observational studies","volume":"378","author":"Matthews AA","year":"2022","unstructured":"Matthews AA, Danaei G, Islam N, et al: Target trial emulation: Applying principles of randomised trials to observational studies. BMJ 378:e071108, 2022","journal-title":"BMJ"},{"key":"e_1_3_7_17_2","doi-asserted-by":"publisher","DOI":"10.1002\/sim.3697"},{"key":"e_1_3_7_18_2","doi-asserted-by":"publisher","DOI":"10.1080\/00273171.2011.568786"},{"key":"e_1_3_7_19_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2016.17700"},{"key":"e_1_3_7_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtho.2018.09.004"},{"key":"e_1_3_7_21_2","doi-asserted-by":"publisher","DOI":"10.21037\/tlcr.2019.03.06"},{"key":"e_1_3_7_22_2","doi-asserted-by":"publisher","DOI":"10.1002\/cam4.4504"},{"key":"e_1_3_7_23_2","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2020.602762"},{"key":"e_1_3_7_24_2","doi-asserted-by":"publisher","DOI":"10.21873\/anticanres.12628"},{"key":"e_1_3_7_25_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrclinonc.2013.158"},{"key":"e_1_3_7_26_2","doi-asserted-by":"publisher","DOI":"10.21037\/tlcr-23-577"}],"container-title":["JCO Oncology Practice"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ascopubs.org\/doi\/pdfdirect\/10.1200\/OP-25-00788","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T21:59:48Z","timestamp":1792015188000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascopubs.org\/doi\/10.1200\/OP-25-00788"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10]]},"references-count":25,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2026,10]]}},"alternative-id":["10.1200\/OP-25-00788"],"URL":"https:\/\/doi.org\/10.1200\/op-25-00788","relation":{},"ISSN":["2688-1527","2688-1535"],"issn-type":[{"value":"2688-1527","type":"print"},{"value":"2688-1535","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10]]},"assertion":[{"value":"2025-08-01","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-09-03","order":1,"name":"revised","label":"Revised","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-11-12","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-12-09","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}