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EGFR-TKI re-administration after osimertinib failure in T790M mutation loss cases with re-biopsy

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Summary

Data on the re-administration of epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) after osimertinib failure in patients with T790M-positive non–small cell lung cancer (NSCLC) is limited. EGFR-TKI re-administration efficacy may vary between patients with T790M loss and those with T790M persistent with re-biopsy after osimertinib treatment. Patients who received EGFR-TKI re-administration (gefitinib, erlotinib, afatinib, dacomitinib, and osimertinib) after osimertinib failure were identified from our database. T790M mutation status before EGFR-TKI re-administration was analyzed via repeat biopsy. We retrospectively evaluated the efficacy of EGFR-TKI re-administration, especially differences according to the T790M mutation status, via repeat biopsy. Until June 2020, 28 patients received EGFR-TKI re-administration and 17 underwent repeat biopsy after osimertinib failure. Patients were divided into three groups, including the T790M loss group, where active mutation persisted and T790M was lost (13/17); T790M remaining group, where both the active mutation and T790M persisted (3/17); and active mutation loss group where both the active mutation and T790M were lost (1/17). The overall response rate (ORR) of EGFR-TKI re-administration in the T790M loss group was 31% and the disease control rate (DCR) was 54%, which were higher than the ORR of 21% and DCR of 43% in the entire patient population. ORR and DCR of the not re-biopsy group were low (9% and 27%, respectively). The therapeutic effect of EGFR-TKI re-administration in patients with T790M-positive NSCLC after osimertinib failure is limited. EGFR-TKI re-administration may be considered in cases of T790M loss after repeat biopsy.

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Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

We thank the patients and their families for their participation in the study. We thank the staff of the Department of Thoracic Medical Oncology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, for supporting this study.

Funding

The authors declare that no funds, grants, or other support were received during the preparation of this manuscript.

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Authors and Affiliations

  1. Department of Thoracic Medical Oncology, the Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan

    Shinsuke Ogusu, Ryo Ariyasu, Takahiro Akita, Ayu Kiritani, Ryosuke Tsugitomi, Yoshiaki Amino, Ken Uchibori, Satoru Kitazono, Noriko Yanagitani & Makoto Nishio

  2. Division of Hematology, Respiratory Medicine and Oncology, Department of Internal Medicine, Faculty of Medicine, Saga University, Saga, Japan

    Shinsuke Ogusu

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  1. Shinsuke Ogusu
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Contributions

(I) Conception and design: Shinsuke Ogusu, Ryo Ariyasu, Makoto Nishio; (II) Provision of study patients: All authors; (III) Data analysis and interpretation: Shinsuke Ogusu, Ryo Ariyasu; (IV) Manuscript writing: All authors; (V) Final approval of manuscript: All authors.

Corresponding author

Correspondence to Makoto Nishio.

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Competing interests

R. Ariyasu reports honoraria from CHUGAI PHARMACEUTICAL CO., Bristol Myers Squib, ONO PHARMACEUTICAL CO., Astrazeneca, outside the submitted work, K. Uchibori reports payment for lectures from DAIICHI SANKYO COMPANY, CHUGAI PHARMACEUTICAL CO., Bristol Myers Squib, ONO PHARMACEUTICAL CO., Astrazeneca, Eli Lilly, Novartis, Thermo Fisher Scientific, Takeda Pharmaceutical Company outside the submitted work. His spouse is an employee of DAIICHI SANKYO. S.Kitazono reports honoraria from Chugai Pharmaceutical Co, Ltd . AstraZeneca, Ono Pharmaceutical, Pfizer, Bristol-Myers Squibb and Merck Sharp & Dohme Corp outside the submitted work. N. Yanagitani reports honoraria from CHUGAI PHARMACEUTICAL CO., Bristol Myers Squib, ONO PHARMACEUTICAL CO., Astrazeneca, Eli Lilly, Takeda Pharmaceutical Company, Pfizer, Bayer Yakuhin, Ltd outside the submitted work. M. Nishio reports grants and personal fees from Ono Pharmaceutical, Bristol Myers Squibb, Pfizer, Chugai Pharmaceutical, Eli Lilly, Taiho Pharmaceutical, AstraZeneca, MSD, Boehringer-Ingelheim, Novartis, Merck Biopharma, Daiichi Sankyo, Takeda Pharmaceutical Company Limited, personal fees from TEIJIN PHARMA LIMITED., AbbVie, outside the submitted work. The remaining authors have not conflicts of interest to declare.

Ethics approval

All procedures performed in studies involving human participants were conducted in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards. This study was approved by the Clinical Research Ethics Committee of Cancer Institute Hospital of JFCR.

Consent to participate

The ethics review board of Cancer Institute Hospital of JFCR approved the present study and permitted the use of the opt-out method in lieu of written informed consent.

Competing interest

R. Ariyasu reports honoraria from CHUGAI PHARMACEUTICAL CO., Bristol Myers Squib, ONO PHARMACEUTICAL CO., Astrazeneca, outside the submitted work, K. Uchibori reports payment for lectures from DAIICHI SANKYO COMPANY, CHUGAI PHARMACEUTICAL CO., Bristol Myers Squib, ONO PHARMACEUTICAL CO., Astrazeneca, Eli Lilly, Novartis, Thermo Fisher Scientific, Takeda Pharmaceutical Company outside the submitted work. His spouse is an employee of DAIICHI SANKYO. S.Kitazono reports honoraria from Chugai Pharmaceutical Co, Ltd. AstraZeneca, Ono Pharmaceutical, Pfizer, Bristol-Myers Squibb and Merck Sharp & Dohme Corp outside the submitted work. N. Yanagitani reports honoraria from CHUGAI PHARMACEUTICAL CO., Bristol Myers Squib, ONO PHARMACEUTICAL CO., Astrazeneca, Eli Lilly, Takeda Pharmaceutical Company, Pfizer, Bayer Yakuhin, Ltd outside the submitted work. M. Nishio reports grants and personal fees from Ono Pharmaceutical, Bristol Myers Squibb, Pfizer, Chugai Pharmaceutical, Eli Lilly, Taiho Pharmaceutical, AstraZeneca, MSD, Boehringer-Ingelheim, Novartis, Merck Biopharma, Daiichi Sankyo, Takeda Pharmaceutical Company Limited, personal fees from TEIJIN PHARMA LIMITED., AbbVie, outside the submitted work. The remaining authors have not conflicts of interest to declare.

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Ogusu, S., Ariyasu, R., Akita, T. et al. EGFR-TKI re-administration after osimertinib failure in T790M mutation loss cases with re-biopsy. Invest New Drugs 40, 1342–1349 (2022). https://doi.org/10.1007/s10637-022-01301-y

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