{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T15:55:02Z","timestamp":1781538902445,"version":"3.54.5"},"reference-count":25,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2026,6,6]],"date-time":"2026-06-06T00:00:00Z","timestamp":1780704000000},"content-version":"vor","delay-in-days":1,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003819","name":"Natural Science Foundation of Hubei Province","doi-asserted-by":"publisher","award":["2025AFB627"],"award-info":[{"award-number":["2025AFB627"]}],"id":[{"id":"10.13039\/501100003819","id-type":"DOI","asserted-by":"publisher"}]},{"name":"China Health & Medical Development Foundation","award":["chmdf2025-xrky07-13"],"award-info":[{"award-number":["chmdf2025-xrky07-13"]}]},{"name":"Beijing Science and Technology Innovation Medical Development Foundation","award":["KC2023-JX-0288"],"award-info":[{"award-number":["KC2023-JX-0288"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,6,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are recommended as the first-line standard treatment for advanced lung adenocarcinoma with common EGFR sensitive mutations (exon 19 E746-A750 deletion and exon 21 L858R). However, the optimal management for rare or compound EGFR mutations remains undefined.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Case presentation<\/jats:title>\n                    <jats:p>We report a case of advanced lung adenocarcinoma with a rare compound EGFR L747S\/L858R mutation. The patient underwent four lines of therapy, showing significant responses to alternating cycles of Osimertinib and Pembrolizumab-chemotherapy, despite intervening disease progression. The clinical course culminated in fatal treatment-induced myelosuppression, with an overall survival exceeding 43\u2009months.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This case underscores dynamic clonal evolution in advanced NSCLC: the initial L747S\/L858R clone showed Osimertinib sensitivity, while subsequent resistance revealed a distinct profile (distinct TP53 mutation, MET amplification, high PD-L1\/TMB) that explained the durable response to Pembrolizumab. These findings provide crucial evidence for sequential therapy strategies in compound EGFR mutations. Our findings also highlight the utility of Next Generation Sequencing (NGS) in identifying targetable resistance mechanisms, enabling prolonged survival in patients with compound EGFR mutations and offering valuable insights for clinical decision-making.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/oncolo\/oyag227","type":"journal-article","created":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T11:42:19Z","timestamp":1780659739000},"source":"Crossref","is-referenced-by-count":0,"title":["Dynamic therapeutic response to osimertinib and immunotherapy in an EGFR L747S and L858R co-mutant NSCLC"],"prefix":"10.1093","volume":"31","author":[{"given":"Yuqing","family":"Tan","sequence":"first","affiliation":[{"name":"Department of Pulmonary Oncology, Zhongnan Hospital, Wuhan University , Wuhan 430071,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tengfei","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Oncology, Zhongnan Hospital, Wuhan University , Wuhan 430071,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Oncology, Zhongnan Hospital, Wuhan University , Wuhan 430071,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7106-9302","authenticated-orcid":false,"given":"Wen","family":"Ouyang","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Oncology, Zhongnan Hospital, Wuhan University , Wuhan 430071,","place":["China"]},{"name":"Hubei Key Laboratory of Tumor Biological Behaviors, Zhongnan Hospital, Wuhan University , Wuhan 430071,","place":["China"]},{"name":"Hubei Clinical Cancer Study Center, Zhongnan Hospital of Wuhan University , Wuhan 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