Impact of First-Line Osimertinib and Other EGFR-Tyrosine Kinase Inhibitors on Overall Survival in Untreated Advanced EGFR-Mutated Non-small Cell Lung Cancer in Japan: Updated Data from TREAD Project 01.

Background: Osimertinib shows higher effectiveness than first-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) in the initial treatment of EGFR-mutated non-small cell lung cancer. However, its superiority in terms of overall survival in the Asian population, especially Japanese patients, remains uncertain.
Objective: To evaluate the survival benefit of osimertinib over other EGFR-TKIs in Japanese patients, using real-world data. METHODS : As part of the Tokushukai REAl-world Data project, a retrospective multi-institutional study across 46 hospitals in Japan was conducted to evaluate the overall survival of patients with advanced EGFR-mutated non-small cell lung cancer using propensity score matching. The study involved patients receiving osimertinib as the first-line treatment (1L-Osi), those initially treated with other EGFR-TKIs (1L-non-Osi), and those receiving osimertinib after initial EGFR-TKI treatment (2L/later-Osi) between April 2010 and December 2022 and followed up until April 2023.
Results: Among 1062 Japanese patients with EGFR-mutated non-small cell lung cancer, 416 (39.2%) received 1L-Osi, while 646 (60.8%) received 1L-non-Osi, including 139 (13.1%) who received 2L/later-Osi. Within these groups, 416 (39.2%), 293 (27.6%), and 75 (7.1%) patients received first-line EGFR-TKI treatment post-osimertinib approval as a later-line treatment in Japan (March 2016). After propensity score matching, the overall survival of the 1L-Osi group was comparable to that of the 1L-non-Osi group in the post-March 2016 subset (n = 283, 42.0 vs 42.4 months). Similar trends were observed in the Del19 and L858R subgroups. The median overall survival of the 2L/later-Osi group was notably long: 60.2 months post-March 2016 (n = 75). A subgroup analysis based on initial EGFR-TKI treatment in the 1L-non-Osi and 2L/later-Osi groups revealed no significant differences among the gefitinib, erlotinib, and afatinib groups.
Conclusions: Based on real-world data, osimertinib did not show a significant improvement in overall survival compared to other EGFR-TKIs as a first-line treatment for EGFR-mutated advanced non-small cell lung cancer in the Japanese (Asian) population.
Clinical Trial Registration: This study was registered at the University Hospital Medical Information Network Clinical Trials Registry on 9 March, 2023 (identification UMIN000050552).
Competing Interests: Declarations Funding No external funding was used in the preparation of this article. Conflict of interest Makoto Hibino received research funding from and engaged in collaborative research with Shionogi & Co., Ltd. outside the submitted work. Tomoya Fukui received speakers’ bureau fees/honoraria from AstraZeneca, Boehringer Ingelheim, Chugai Pharm, Eli Lilly, Nippon Kayaku, Novartis Pharma, Ono Pharm, Pfizer, and Taiho Pharm outside the submitted work. Imamura received speakers’ bureau fees/honoraria from Bayer, Bristol-Myers Squibb, Daiichi-Sankyo, Pfizer, and Ono Pharm outside the submitted work. Minami received speakers’ bureau fees/honoraria from Daiichi-Sankyo and Ono Pharm; research funding from Astelas-Amgen Biopharma, Bayer, Bristol-Myers Squibb, Chugai, Daiichi-Sankyo, Incite, Novartis, Ono Pharm, Pfizer, and Rakuten Medical; and scholarship donations from Bayer, Chugai, Daiichi-Sankyo, Eisai, Kyowa-Kirin, Lilly, Ono Pharmaceutical, Pfizer, Taiho Pharma, and Takeda outside the submitted work. These organizations had no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; and in the decision to submit the article for publication. Rai Shimoyama, Ryuta Fukai, Akihiko Iwase, Yukihiro Tamura, Yusuke Chihara, Takafumi Okabe, Uryu Kiyoaki, Tadahisa Okuda, and Masataka Taguri have no conflicts of interest that are directly relevant to the content of this article. Ethics approval The study was conducted following the principles of the Declaration of Helsinki and was reviewed and approved by the Ethics Committee of the Tokushukai Group on 2 March, 2023 (approval number: TGE 01427-008). This study was registered at the University Hospital Medical Information Network Clinical Trials Registry on 9 March, 2023 (identification UMIN000050552). Consent to participate The requirement for obtaining informed consent from patients was waived because this was a retrospective analysis of anonymized patient data. Patients were allowed to opt out of the research use of their data, and related information is publicly available on the Tokushukai Medical Group website. Consent for publication Not applicable. Availability of data and material The data supporting the findings of this study are available from the corresponding author on reasonable request. Code availability Not applicable. Authors’ contributions Conceptualization, data curation, formal analysis, investigation, methodology, resources, writing (original draft): MH. Resources, writing (review and editing): KU. Resources, writing (review and editing): RS. Resources, writing (review and editing): TF. Resources, writing (review and editing): RF. Resources, writing (review and editing): AI. Resources, writing (review and editing): YT. Resources, writing (review and editing): YC. Resources, writing (review and editing): MF. Formal analysis: TO. Formal analysis: MT. Writing (review and editing): YI. Writing (review and editing): HM.
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