Abstract
The EXTRA trial was the first to identify predictive biomarkers for afatinib efficacy in epidermal growth factor receptor (EGFR)-mutant NSCLC. We analyzed the clinical data of older adult patients before translational analysis. This prospective study involved untreated patients with EGFR-mutant NSCLC who received afatinib at an initial dose of 40 mg/day, followed by stepwise dose reductions, ultimately reaching 20 mg administered every other day. Treatment efficacy and adverse events (AEs) were compared between non-older and older adult patients. Among the 103 patients, 71 were aged < 75 years, and 32 were aged ≥ 75 years. Despite increased dose reductions in the older adults, progression-free survival was comparable: 21.5 vs. 18.6 months for non-older and older adults, respectively. The median overall survival (OS) was not reached in either group; the 2-year OS rates were 82% and 75% in non-older and older adults, respectively. Median post-progression survival in patients administered second-line drug therapy was 14.3 and 11.2 months in non-older (n = 42) and older adults (n = 20), respectively. Among older adults, 31 (97%) patients experienced AEs of all grades, and only six patients had grade ≥ 3 AEs with no grade 5 AEs. Afatinib demonstrated comparable therapeutic efficacy and safety in older and non-older adult patients with advanced EGFR-mutant NSCLC.
Trial registration: UMIN-CTR identifier (UMIN000024935)
Data availability
All data generated or analysed during this study are included in this published article and its Supplementary Information file.
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Acknowledgements
The authors would like to thank all the patients who participated in this study and their families, as well as the investigators.
Funding
Nippon Boehringer Ingelheim Co., Ltd.
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Kei Morikawa, Original draft writing, Resources, review & editing, Saori Takata, Resources, Writing, Writing—review editing, Hisashi Tanaka, Resources, Writing—review & editing, Hidetoshi Itani, Resources, Writing—review & editing, Masashi Ishihara, Resources, Writing—review & editing, Kazuya Horiuchi, Resources, Writing—review & editing, Yasuhiro Kato, Resources, Writing—review & editing, Shinnosuke Ikemura, Resources, Writing—review & editing, Hideyuki Nakagawa, Resources, Writing—review & editing, Yoshiro Nakahara, Resources, Writing—review & editing, Yoshitaka Seki, Resources, Writing—original draft, Writing—review & editing, Akihiro Bessho, Resources, Writing—review & editing, Nobumasa Takahashi, Resources, Writing—review & editing, Kentaro Hayashi, Resources, Writing—review & editing, Takeo Endo, Resources, Writing—review & editing, Kiyoshi Takeyama, Resources, Writing—review & editing, Toshiya Maekura, Resources, Writing—review & editing, Nagio Takigawa, Resources, Writing—original draft, Writing—review & editing, Akikazu Kawase, Resources, Writing—review & editing, Makoto Endoh, Resources, Writing—review & editing, Kenji Nemoto, Resources, Writing—review & editing, Kazuma Kishi, Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Project administration, Validation, Writing—original draft, Writing—review & editing, Kenzo Soejima, Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Project administration, Validation, Writing—original draft, Writing—review & editing, Yusuke Okuma, Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Project administration, Validation, Writing—original draft, Writing—review & editing, Kenichi Yoshimura, Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Validation, Writing—original draft, Writing—review & editing, Daisuke Saigusa, Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Project administration, Validation, Writing—original draft, Writing—review & editing, Yae Kanai, Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Project administration, Validation, Writing—original draft, Writing—review & editing, Koji Ueda, Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Project administration, Validation, Writing—original draft, Writing—review & editing, Akira Togashi, Conceptualization, Methodology, Project administration, Writing—review & editing, Noriyuki Matsutani, Conceptualization, Data curation, Formal analysis, Funding acquisition, Investigation, Methodology, Project administration, Validation, Writing—original draft, Writing—review & editing, and Nobuhiko Seki, Conceptualization, Data curation, Formal analysis, Funding acquisition, Investigation, Methodology, Project administration, Validation, Writing—original draft, Writing—review & editing.
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Kei Morikawa: personal fees as honoraria from AstraZeneca, Boehringer Ingelheim, Chugai Pharmaceutical, Eli Lilly, Takeda Pharmaceutical; Hisashi Tanaka: personal fees as honoraria from Ono Pharmaceutical, Bristol Myers Squibb, AstraZeneca, Chugai Pharmaceutical, Boehringer Ingelheim, and Pfizer; Yoshitaka Seki: personal fees as honoraria from AstraZeneca, Eli Lilly, MSD, Ono Pharmaceutical, Novartis, Taiho Pharmaceutical, Chugai Pharmaceutical, Boehringer Ingelheim, Shionogi, Sanofi, Kyowa Kirin, Kyorin Pharmaceutical, and GSK; Nagio Takigawa: personal fees as honoraria from Boehringer-Ingelheim Japan, Chugai Pharmaceutical, Eli Lilly Japan, Ono Pharmaceutical, AstraZeneca, Bristol-Myers Squibb Company Japan, Daiichi-Sankyo Pharmaceutical, Taiho Pharmaceutical, Pfizer Inc. Japan, Nippon Kayaku Co. Ltd., Takeda Pharmaceutical Co. Ltd., MSD, and Kyowa Hakko Kirin. Kazuma Kishi: research funding and personal fees as honoraria from Boehringer Ingelheim; Yusuke Okuma: research funding, advisory fee, and personal fees as honoraria from AstraZeneca; research funding from AbbVie and Merck Sharp & Dohme; and personal fees as honoraria from and Chugai Pharmaceutical, Eisai, Eli Lilly, MSD, Ono Pharmaceutical, Takeda Pharmaceutical, and Taiho Pharmaceutical; Akira Togashi: employee of Boehringer Ingelheim; Nobuhiko Seki: research funding and personal fees as honoraria from Eli Lilly, Ono Pharmaceutical, Boehringer Ingelheim, Taiho Pharmaceutical, Chugai Pharmaceutical, Takeda Pharmaceutical, Nippon Kayaku, Pfizer, and Daiichi Sankyo; research funding from Eisai and Shionogi; and personal fees as honoraria from AstraZeneca, MSD, Bristol Myers Squibb, Novartis, and Kyowa Kirin. No potential conflicts of interest were disclosed by the other authors.
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Morikawa, K., Takata, S., Tanaka, H. et al. Efficacy and safety findings of the EXTRA study in older adult EGFR-mutant lung cancer patients receiving afatinib as first-line treatment. Sci Rep (2026). https://doi.org/10.1038/s41598-026-38944-3
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DOI: https://doi.org/10.1038/s41598-026-38944-3
