{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T22:11:30Z","timestamp":1791411090292,"version":"4.3.3"},"reference-count":23,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"18","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["JCO"],"published-print":{"date-parts":[[2025,6,20]]},"abstract":"<jats:sec>\n            <jats:title>PURPOSE<\/jats:title>\n            <jats:p>\n              To our knowledge, the ACHILLES\/TORG1834 trial is the first randomized study comparing afatinib and chemotherapy in patients with non\u2013small cell lung cancer (NSCLC) harboring sensitizing uncommon epidermal growth factor receptor (\n              <jats:italic toggle=\"yes\">EGFR<\/jats:italic>\n              ) mutations.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>METHODS<\/jats:title>\n            <jats:p>\n              This randomized, open-label study was performed at 51 Japanese institutions and recruited treatment-na\u00efve patients with nonsquamous NSCLC with uncommon\n              <jats:italic toggle=\"yes\">EGFR<\/jats:italic>\n              mutations, excluding exon 20 insertions and T790M mutations. Patients were randomly assigned 2:1 to receive afatinib (30 or 40 mg orally, at the treating physician's discretion) or a combination of platinum (cisplatin or carboplatin) and pemetrexed, followed by pemetrexed maintenance. The primary end point was progression-free survival (PFS). Secondary end points included objective response rate (ORR), overall survival, and safety. A prespecified interim analysis was planned to provide clinically meaningful information promptly, along with a crossover recommendation if necessary.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>RESULTS<\/jats:title>\n            <jats:p>\n              A total of 109 patients were enrolled between March 2019 and February 2023. In the interim analysis, the Data and Safety Monitoring Committee recommended early study termination. The median PFS was significantly longer in patients receiving afatinib than in those undergoing chemotherapy (10.6\n              <jats:italic toggle=\"yes\">v<\/jats:italic>\n              5.7 months; hazard ratio, 0.421 [95% CI, 0.251 to 0.706];\n              <jats:italic toggle=\"yes\">P<\/jats:italic>\n              = .0010). ORRs to afatinib were similar across the overall population and among participants with major uncommon (G719X, L861Q, and S768I), compound, and other mutations (61.7%, 55.8%, 72.7%, and 60.0%, respectively). The most common grade 3 or higher adverse events were diarrhea, paronychia, and rash for afatinib, and appetite loss and nausea for chemotherapy.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>CONCLUSION<\/jats:title>\n            <jats:p>\n              Afatinib should be considered the standard initial therapy for patients with NSCLC with sensitizing uncommon\n              <jats:italic toggle=\"yes\">EGFR<\/jats:italic>\n              mutations.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1200\/jco-24-02007","type":"journal-article","created":{"date-parts":[[2025,4,16]],"date-time":"2025-04-16T19:59:05Z","timestamp":1744833545000},"page":"2049-2058","update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":34,"title":["Pragmatic Randomized Study of Afatinib Versus Chemotherapy for Patients With Non\u2013Small Cell Lung Cancer With Uncommon Epidermal Growth Factor Receptor Mutations: ACHILLES\/TORG1834"],"prefix":"10.1200","volume":"43","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7868-6661","authenticated-orcid":true,"given":"Satoru","family":"Miura","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Niigata Cancer Center Hospital, Niigata, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Tanaka","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Niigata Cancer Center Hospital, Niigata, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8339-2895","authenticated-orcid":true,"given":"Toshihiro","family":"Misumi","sequence":"additional","affiliation":[{"name":"Department of Data Science, National Cancer Center Hospital East, Chiba, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7724-0481","authenticated-orcid":false,"given":"Hiroshige","family":"Yoshioka","sequence":"additional","affiliation":[{"name":"Department of Thoracic Oncology, Kansai Medical University Hospital, Osaka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takaaki","family":"Tokito","sequence":"additional","affiliation":[{"name":"Division of Respirology, Neurology, and Rheumatology, Department of Internal Medicine, Kurume University School of Medicine, Fukuoka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0440-470X","authenticated-orcid":true,"given":"Tatsuro","family":"Fukuhara","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, Miyagi Cancer Center, Natori-shi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7829-7524","authenticated-orcid":true,"given":"Yuki","family":"Sato","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, Kobe City Medical Center General Hospital, Kobe-shi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5015-193X","authenticated-orcid":true,"given":"Yoshimasa","family":"Shiraishi","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9637-1388","authenticated-orcid":true,"given":"Katsuhiko","family":"Naoki","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, Kitasato University School of Medicine, Sagamihara-shi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5856-5512","authenticated-orcid":true,"given":"Hiroaki","family":"Akamatsu","sequence":"additional","affiliation":[{"name":"Internal Medicine III, Wakayama Medical University, Wakayama, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7194-6459","authenticated-orcid":true,"given":"Ou","family":"Yamaguchi","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, Saitama Medical University International Medical Center, Saitama, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshihide","family":"Yokoyama","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, Kurashiki Central Hospital, Okayama, 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