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Osimertinib for patients with poor performance status and EGFR T790M mutation-positive advanced non-small cell lung cancer: a phase II clinical trial

  • PHASE II STUDIES
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Summary

Osimertinib is a molecularly targeted agent used to treat non-small cell lung cancer (NSCLC) patients with an epidermal growth factor receptor (EGFR) T790M mutation. However, its efficacy and safety profile when patients have poor performance status (PS) is unknown. Therefore, we conducted an open-label, multi-center, single-arm phase II study to evaluate its efficacy and safety in EGFR T790M mutation-positive NSCLC patients with Eastern Cooperative Oncology Group PS scores of between 2 and 4. Patients received 80 mg of osimertinib once daily. Our primary endpoint was progression-free survival. Eighteen patients were enrolled between June 2017 and November 2018. The median age was 77 years (range: 55–85 years). Ten, six, and two patients had PS scores of 2, 3, and 4, respectively. All patients had adenocarcinoma with common EGFR mutations and had been treated with first- or second-generation EGFR- tyrosine kinase inhibitors previously. The overall median progression-free survival was 7.0 months (90% confidence interval: 5.5–8.9 months). The overall response rate and median overall survival were 53% and 12.7 months, respectively. Moreover, improved PS scores were observed in 72% of the patients. Although the incidence of grade 3 adverse events was low, with no grade 4 or 5 events observed, three patients required treatment cessation due to the development of interstitial lung disease. Osimertinib therapy could be beneficial for EGFR T790M mutation-positive advanced NSCLC patients with poor PS. This trial was registered with the Japan Registry of Clinical Trials on March 12, 2019 (trial no. jRCT1041180081).

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Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors

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Authors and Affiliations

  1. Division of Thoracic Oncology, Shizuoka Cancer Center, Shizuoka, Japan

    Kazuhisa Nakashima, Takahisa Kawamura, Toshiaki Takahashi & Haruyasu Murakami

  2. Department of Internal Medicine, Division of Medical Oncology & Respiratory Medicine, Shimane University Faculty of Medicine, 89-1 Enya-cho, Izumo, Shimane, Japan

    Kazuhisa Nakashima

  3. Internal Medicine III, Wakayama Medical University, Wakayama, Japan

    Yuichi Ozawa, Hiroaki Akamatsu & Nobuyuki Yamamoto

  4. Department of Medical Oncology, Osaka City General Hospital, Osaka, Japan

    Haruko Daga & Yuko Tsuboguchi

  5. Division of Respiratory Medicine, Gunma Prefectural Cancer Center, Ota, Gunma, Japan

    Hisao Imai

  6. Department of Thoracic Oncology, Osaka International Cancer Institute, Osaka, Japan

    Motohiro Tamiya

  7. Department of Medicine, Division of Respirology, Neurology, and Rheumatology, Kurume University School of Medicine, Fukuoka, Japan

    Takaaki Tokito

  8. Clinical Research Center, Shizuoka Cancer Center, Shizuoka, Japan

    Keita Mori

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  1. Kazuhisa Nakashima
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  2. Yuichi Ozawa
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Contributions

Kazuhisa Nakashima (Corresponding Author): creating the study protocol, recruitment of patients, and writing the manuscript; Yuichi Ozawa: recruitment of patients and reviewing the manuscript; Haruko Daga: recruitment of patients and reviewing the manuscript; Hisao Imai: recruitment of patients and reviewing the manuscript; Motohiro Tamiya: recruitment of patients and reviewing the manuscript; Takaaki Tokito: recruitment of patients and reviewing the manuscript; Takahisa Kawamura: recruitment of patients and reviewing the manuscript; Hiroaki Akamatsu: recruitment of patients and reviewing the manuscript; Yuko Tsuboguchi: recruitment of patients and reviewing the manuscript; Toshiaki Takahashi: recruitment of patients and reviewing the manuscript; Nobuyuki Yamamoto: recruitment of patients and reviewing the manuscript; Keita Mori (Primary biostatistician of the study): creating the study protocol, statistical analysis, and reviewing the manuscript; Haruyasu Murakami: creating the study protocol, recruitment of patients, and writing the manuscript.

Corresponding author

Correspondence to Kazuhisa Nakashima.

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Conflict of interest

Kazuhisa Nakashima declares that he has no conflict of interest. Yuichi Ozawa had received personal fees from AstraZeneca, Boehringer Ingelheim, and Chugai Pharma. Haruko Daga had received personal fees from Boehringer Ingelheim, Chugai Pharma, and Ono Pharmaceutical, and grants from Astella, Pfizer, and Taiho Pharmaceutical. Hisao Imai declares that he has no conflict of interest. Motohiro Tamiya had received personal fees from Asahi Kasei Pharmaceutical, AstraZeneca, Chugai Pharma, Eli Lilly, MSD, and Taiho Pharmaceutical, and personal fees and grants from Boehringer Ingelheim, Bristol-Myers Squibb, and Ono Pharmaceutical. Takaaki Tokito had received personal fees from AstraZeneca, Boehringer Ingelheim, and Chugai Pharma. Takahisa Kawamura declares that he has no conflict of interest. Hiroaki Akamatsu had received personal fees from AstraZeneca, Boehringer Ingelheim, Chugai Pharma, and Pfizer. Yuko Tsuboguchi declares that he has no conflict of interest. Toshiaki Takahashi had received personal fees from Boehringer Ingelheim and Roche Diagnostics K.K., grants from Japan Agency for Medical Research and Development, and personal fees and grants from AstraZeneca, Chugai Pharma, Eli Lilly, MSD, Ono Pharmaceutical, and Pfizer. Nobuyuki Yamamoto had received personal fees from AstraZeneca, and personal fees and grants from Boehringer Ingelheim and Chugai Pharma. Keita Mori declares that he has no conflict of interest. Haruyasu Murakami had received personal fees from Bristol-Myers Squibb, Ono Pharmaceutical, and MSD, grants from Abbvie, Daiichi Sankyo, and IQvia, and personal fees and grants from AstraZeneca, Chugai Pharma, Eli Lilly, Taiho Pharmaceutical, and Takeda.

Ethics approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional review board and the 1964 Helsinki declaration and its later amendments or with comparable ethical standards. This trial was registered with the Japan Registry of Clinical Trials on March 12, 2019 (trial no. jRCT1041180081).

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Informed consent was obtained from all individual participants included in the study.

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Nakashima, K., Ozawa, Y., Daga, H. et al. Osimertinib for patients with poor performance status and EGFR T790M mutation-positive advanced non-small cell lung cancer: a phase II clinical trial. Invest New Drugs 38, 1854–1861 (2020). https://doi.org/10.1007/s10637-020-00943-0

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