{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T15:06:48Z","timestamp":1790089608697,"version":"4.0.1"},"reference-count":33,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T00:00:00Z","timestamp":1787788800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Dongguan Social Development Science and Technology","award":["20221800906342"],"award-info":[{"award-number":["20221800906342"]}]},{"name":"Beijing Kangmeng Charity Foundation Medical Research Development Fund"},{"name":"Clinical and Basic Research Special Program","award":["TB219009"],"award-info":[{"award-number":["TB219009"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,9,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The standard first-line treatment for advanced EGFR-mutated non-small cell lung cancer (NSCLC) is EGFR tyrosine kinase inhibitors. However, concurrent mutations facilitate resistance evolution in EGFR-mutant lung adenocarcinoma and combination therapies may offer a superior approach. This study explores the efficacy and safety of osimertinib plus anlotinib as first-line treatment for advanced NSCLC with EGFR co-mutations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>This study prospectively enrolled patients with advanced NSCLC harboring EGFR (19Del\/21L858R) mutations and \u22651 mutation in TP53, PIK3CA, or RB1, who had not undergone systemic treatment. Kaplan-Meier survival analysis tested the differences among patients with different concurrent mutations. ctDNA test was administered before and after treatment and its correlation with efficacy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>A total of 38 patients were enrolled, with co-mutations in TP53 (76.3%), PIK3CA (26.3%), and RB1 (2.6%). With a median follow-up of 25.6\u2009months, the median progression-free survival (PFS) was 29.0\u2009months (95% CI, 18.6-NR), and 1-year PFS rate was 85% (95% CI, 70.4%-94.5%). Objective response rate was 73.7% (95% CI, 56.9%-86.3%), and disease control rate was 100.0% (95% CI, 90.7%-100.0%). Adverse events of any grade occurred in all patients. Seven (18.4%) patients experienced grade 3 treatment-related adverse events (TRAEs), with no grade 4 TRAEs or treatment-related deaths.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Osimertinib plus anlotinib shows promising efficacy and manageable toxicity as first-line treatment for advanced NSCLC with EGFR co-mutations (ChiCTR2300070023).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Clinical trial registration<\/jats:title>\n                    <jats:p>This study was registered in the Chinese Clinical Trial Registry (ChiCTR) under the registration number ChiCTR2300070023 on March 31, 2023 (https:\/\/www.chictr.org.cn).<\/jats:p>\n                  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