{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T19:22:38Z","timestamp":1767986558134,"version":"3.49.0"},"reference-count":17,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2025,12,5]],"date-time":"2025-12-05T00:00:00Z","timestamp":1764892800000},"content-version":"vor","delay-in-days":4,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Reports"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Epidermal growth factor receptor (EGFR) mutations are detected in approximately 40%\u201350% of patients with lung adenocarcinoma in Asian populations and in around 10% of patients in Western populations. Among these, the EGFR L861R mutation is uncommon and undetectable using conventional polymerase chain reaction methods. Recently, clinically available next\u2010generation sequencing (NGS) has been used to detect L861R mutations, potentially increasing the number of identified cases of L861R\u2010positive non\u2010small cell lung cancer. Herein, we present two cases of EGFR L861R\u2010mutated lung adenocarcinoma treated with afatinib and osimertinib to evaluate the clinical efficacy and tolerability of these targeted therapies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Case<\/jats:title>\n                    <jats:p>Case 1: A 63\u2010year\u2010old man with lung adenocarcinoma harboring an EGFR L861R mutation (cStage IVB) received afatinib 40\u2009mg\/day. Computer tomography (CT) on Day 49 showed shrinkage of the primary tumor, accompanied by a decrease in tumor markers. The afatinib dose was reduced to 30\u2009mg\/day due to Grade 1 diarrhea and an acneiform rash. Ground\u2010glass opacities were subsequently observed around the tumor. Although pneumonitis was initially suspected, the findings were subsequently considered consistent with carcinomatous lymphangitis. Consequently, afatinib was discontinued on Day 56. Case 2: An 83\u2010year\u2010old man with lung adenocarcinoma harboring an EGFR L861R mutation (cStage IVB) received osimertinib 80\u2009mg\/day. Afatinib was avoided due to concerns regarding tolerability in the elderly. CT imaging on Day 14 showed tumor shrinkage with reduced attenuation and decreased levels of tumor markers. However, osimertinib was discontinued on Day 104 due to a Grade 3 skin rash. The response to osimertinib was evaluated as stable disease. Following treatment discontinuation, the disease progressed to multiple brain metastases, and supportive care was initiated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Here, we present the first case showing the anti\u2010tumor efficacy of afatinib and the second case showing the anti\u2010tumor efficacy of osimertinib in a patient with EGFR L861R\u2010positive lung adenocarcinoma. Despite their short treatment durations, afatinib and osimertinib may have potential clinical activity in patients with EGFR L861R\u2010positive lung cancer.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cnr2.70420","type":"journal-article","created":{"date-parts":[[2025,12,6]],"date-time":"2025-12-06T02:39:44Z","timestamp":1764988784000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Two Cases of Epidermal Growth Factor Receptor\n                    <scp>L861R<\/scp>\n                    Mutation\u2010Positive Lung Adenocarcinoma Treated With Osimertinib and Afatinib"],"prefix":"10.1002","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-9910-0109","authenticated-orcid":false,"given":"Kei","family":"Kagawa","sequence":"first","affiliation":[{"name":"Department of Respiratory Medicine Hiroshima University Hospital  Hiroshima Japan"},{"name":"Department of Respiratory Medicine Chugoku Rosai Hospital  Kure Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3557-0049","authenticated-orcid":false,"given":"Takeshi","family":"Masuda","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine Hiroshima University Hospital  Hiroshima Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5382-4730","authenticated-orcid":false,"given":"Kiyofumi","family":"Shimoji","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine Hiroshima University Hospital  Hiroshima Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9117-1934","authenticated-orcid":false,"given":"Kakuhiro","family":"Yamaguchi","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine Hiroshima University Hospital  Hiroshima Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2805-900X","authenticated-orcid":false,"given":"Shinjiro","family":"Sakamoto","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine Hiroshima University Hospital  Hiroshima Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3390-8491","authenticated-orcid":false,"given":"Yasushi","family":"Horimasu","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine Hiroshima University Hospital  Hiroshima Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0035-674X","authenticated-orcid":false,"given":"Taku","family":"Nakashima","sequence":"additional","affiliation":[{"name":"Department of Molecular and Internal Medicine, Graduate School of Biomedical and Health Sciences Hiroshima University  Hiroshima Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0516-4341","authenticated-orcid":false,"given":"Hiroshi","family":"Iwamoto","sequence":"additional","affiliation":[{"name":"Department of Molecular and Internal Medicine, Graduate School of Biomedical and Health Sciences Hiroshima University  Hiroshima Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7979-0708","authenticated-orcid":false,"given":"Hironobu","family":"Hamada","sequence":"additional","affiliation":[{"name":"Department of Physical Analysis and Therapeutic Sciences Hiroshima University  Hiroshima Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8234-942X","authenticated-orcid":false,"given":"Noboru","family":"Hattori","sequence":"additional","affiliation":[{"name":"Department of Molecular and Internal Medicine, Graduate School of Biomedical and Health Sciences 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