{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T21:43:39Z","timestamp":1790113419640,"version":"4.0.1"},"reference-count":30,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T00:00:00Z","timestamp":1767916800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Epidermal growth factor receptor (EGFR) exon 20 insertion (ex20ins)-mutant non-small cell lung cancer (NSCLC) is characterized by limited sensitivity to standard-dose EGFR tyrosine kinase inhibitors (EGFR-TKIs) and historically poor clinical outcomes. Although agents such as amivantamab and other targeted therapies have expanded treatment options, access barriers and marked variant-specific heterogeneity remain major challenges. Emerging evidence suggests that dose-escalated third-generation EGFR-TKIs may provide clinical benefit in selected ex20ins subtypes, yet real-world data are scarce.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Case presentation<\/jats:title>\n                    <jats:p>\n                      We describe a 56-year-old never-smoking female with metastatic lung adenocarcinoma harboring an EGFR A767_V769dup exon 20 insertion and co-mutations in\n                      <jats:italic>TP53, SETD2, SMAD4<\/jats:italic>\n                      , and\n                      <jats:italic>ETV6<\/jats:italic>\n                      , with low PD-L1 expression. In the setting of limited access to amivantamab at diagnosis and preliminary evidence supporting intensified EGFR inhibition in certain \u201cnear-loop\u201d ex20ins variants, the patient received off-label high-dose osimertinib 160 mg once daily as first-line therapy. She achieved a durable partial response with manageable Grade 1 skin and nail toxicities and no dose reductions. Following disease progression, and after multidisciplinary discussion and informed consent, she was switched to off-label furmonertinib 240 mg once daily, resulting in additional disease control. Sequential high-dose osimertinib followed by high-dose furmonertinib yielded an overall survival of approximately 37 months.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Literature and trend overview<\/jats:title>\n                    <jats:p>To contextualize this case, we conducted a targeted narrative review and a descriptive bibliometric overview using CiteSpace (2000\u20132023) based on Web of Science Core Collection records. This analysis demonstrated a growing global research focus on third-generation EGFR-TKIs and variant-specific treatment strategies for EGFR ex20ins-mutant NSCLC, supporting the rationale underpinning the therapeutic approach adopted in this report.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Sequential high-dose third-generation EGFR-TKIs may offer clinically meaningful benefit in selected EGFR ex20ins cases; however, this strategy remains non-standard and should be regarded as hypothesis-generating, warranting further prospective evaluation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmed.2025.1677737","type":"journal-article","created":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T06:41:15Z","timestamp":1767940875000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Prolonged survival in EGFR exon 20 insertion mutant lung adenocarcinoma: case report of sequential osimertinib and furmonertinib with research trend 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