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Apixaban in Japanese patients with cancer-associated venous thromboembolism: a multi-center phase II trial

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Abstract

Background

Recent pivotal phase III trials involving direct oral anticoagulant (DOAC) versus low molecular weight heparin have demonstrated the utility of DOACs in Western patients with cancer-associated venous thromboembolism (VTE). However, these trials did not include Japanese patients. This phase II trial evaluated the safety and efficacy of apixaban in Japanese patients with cancer-associated VTE (UMIN000028447).

Method and results

Apixaban was initiated at 10 mg twice daily for 7 days, followed by 5 mg twice daily for 23 weeks. The primary endpoint was the incidence of major or clinically relevant non-major (CRNM) bleeding events during the treatment period. The study was terminated due to safety concerns after enrolling 27 patients. Median age was 71 years; median body weight was 51.3 kg; and major primary tumor sites were the gastrointestinal tract (26%) and lung (19%). During the median follow-up period of 5.4 months, major or CRNM bleeding occurred in in 26% of patients (major, n = 5; CRNM, n = 2; 95% confidence interval, 11–46%). No recurrent VTE or VTE-related death occurred. Estimated overall survival at 6 months was 68%.

Conclusion

This study demonstrated the excessive bleeding risk of apixaban at the standard dose in Japanese patients with cancer-associated VTE.

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Acknowledgements

This study was funded by the Training Plan for Oncology Professionals, Japan. The funding source had no role in the planning, conduct or reporting of this paper.

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Authors and Affiliations

  1. Medical Oncology/Hematology, Kobe University Hospital, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan

    Yoshinori Imamura, Taku Nose, Shinya Ohata, Yoshiharu Miyata, Yohei Funakoshi, Masanori Toyoda, Kimikazu Yakushijin, Naomi Kiyota, Hiroshi Matsuoka & Hironobu Minami

  2. General Internal Medicine, Kobe University Hospital, Kobe, Japan

    Kazunori Otsui & Kenta Mori

  3. Medical Oncology, Kobe Minimally Invasive Cancer Center, Kobe, Japan

    Koichi Kitagawa & Hideaki Okada

  4. Thoracic Oncology, Kobe Minimally Invasive Cancer Center, Kobe, Japan

    Akito Hata

  5. Medical Oncology, Kindai University Faculty of Medicine, Osakasayama, Japan

    Hidetoshi Hayashi

  6. Cancer Center, Kobe University Hospital, Kobe, Japan

    Naomi Kiyota & Hironobu Minami

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  1. Yoshinori Imamura
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Correspondence to Yoshinori Imamura.

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Conflict of interest

Yoshinori Imamura has received speakers’ bureau/honoraria from Bayer, Bristol-Myers Squibb, Daiichi-Sankyo, and Pfizer. Kazunori Otsui has received speakers’ bureau/honoraria from Bayer, Bristol-Myers Squibb, Daiichi-Sankyo, and Pfizer. Akito Hata has received speakers’ bureau/honoraria from Bristol-Myers Squibb, Daiichi-Sankyo, and Pfizer. Hidetoshi Hayashi has received speakers’ bureau/honoraria and research grant support from Bristol-Myers Squibb, Daiichi-Sankyo, and Pfizer. Kimikazu Yakushijin has received speakers’ bureau/honoraria from Pfizer. Kiyota Naomi has received speakers’ bureau/honoraria from Bayer and Bristol-Myers Squibb and research grant support from Bayer, Bristol-Myers Squibb, and Pfizer. Hiroshi Matsuoka has received speakers’ bureau/honoraria from Bristol-Myers Squibb and Pfizer. Hironobu Minami has received speakers’ bureau/honoraria from Bayer, Bristol-Myers Squibb, Daiichi-Sankyo, and Pfizer and research grant support from Bayer, Bristol-Myers Squibb, Daiichi-Sankyo, and Pfizer. The other authors declare that they have no conflict of interest in the submitted work.

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Imamura, Y., Otsui, K., Mori, K. et al. Apixaban in Japanese patients with cancer-associated venous thromboembolism: a multi-center phase II trial. Int J Hematol 115, 499–507 (2022). https://doi.org/10.1007/s12185-022-03289-w

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