https://bbwpublisher.com/index.php/PAR <p style="text-align: justify;"><em>Proceedings of Anticancer Research (PAR)&nbsp;</em>is an international peer-reviewed and open access journal, which is devoted to the rapid publication of high-quality original articles, reviews, case reports, short communication and letters on all aspects of experimental and clinical oncology.</p> <p style="text-align: justify;">The covered topics include, but are not limited to:&nbsp;cellular research and bio-markers, identification of bio-targets and agents with novel mechanisms of action, preventative and integrated treatments for cancer patients, radiation and surgery, palliative care, patient adherence, quality of life, satisfaction, and anticancer medicine,&nbsp;anticancer agents,&nbsp;novel therapies in development,&nbsp;cancer management,&nbsp;biomarkers,&nbsp;diagnostics,&nbsp;clinical trials,&nbsp;treatment guidelines.</p> <p align="justify">&nbsp;</p> Bio-Byword Scientific Publishing PTY LTD en-US Proceedings of Anticancer Research 2208-3545 https://bbwpublisher.com/index.php/PAR/article/view/12116 <p><em>Background</em>: Leptomeningeal metastasis (LM) after third-generation EGFR-TKIs resistance carries a dismal prognosis. Limited blood–brain-barrier penetration rather than secondary EGFR mutations is the dominant resistance mechanism. We report a case managed with CNS-penetrant EGFR inhibition of zorifertinib. <em>Method</em>: A 53-year-old, never-smoking woman with EGFR L858R-mutant stage IVb non-small-cell lung cancer (NSCLC) developed LM after progression on osimertinib 160 mg and firmonertinib 160 mg. Salvage therapy with zorifertinib (200 mg BID) plus firmonertinib (80 mg qd) was initiated. <em>Results</em>: Within 14 days, the coma resolved. Karnofsky Performance Status improved from 20 to 70. Serial imaging at 3 and 5 months revealed stable disease with shrinkage according to RECIST 1.1. Only grade 1–2 diarrhea, rash, and transaminitis occurred and resolved with symptomatic care. <em>Conclusion: </em>The combination of zorifertinib plus firmonertinib provides durable intracranial control and rapid neurological recovery after third-generation EGFR-TKI failure. Prospective validation is warranted.</p> Ye Wang Deliang Huang Copyright (c) 2025 Author(s) 2025-09-30 2025-09-30 9 5 1 8 10.26689/par.v9i5.12116