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Randomized Controlled Trial
. 2019 Aug;98(32):e16770.
doi: 10.1097/MD.0000000000016770.

Efficacy of denosumab for restoring normal bone mineral density in women receiving adjuvant aromatase inhibitors for early breast cancer

Koichi Sakaguchi  1 , Hisako Ono  1   2 , Katsuhiko Nakatsukasa  3 , Takashi Ishikawa  4 , Yoshie Hasegawa  5 , Masato Takahashi  6 , Naoki Niikura  7 , Kei Koizumi  8 , Teruhisa Sakurai  9 , Hideo Shigematsu  10 , Shunji Takahashi  11 , Shinichiro Taira  11 , Masato Suzuki  12 , Kazutaka Narui  13 , Daishu Miura  14 , Kimito Yamada  4 , Mana Yoshimura  15 , Hisashi Shioya  16 , Eiichi Konishi  17 , Yokota Isao  18 , Kojiro Imai  19 , Kei Fujikawa  20 , Tetsuya Taguchi  1 ; Collaborative Study Group of Scientific Research of the Japanese Breast Cancer Society
Affiliations
Randomized Controlled Trial

Efficacy of denosumab for restoring normal bone mineral density in women receiving adjuvant aromatase inhibitors for early breast cancer

Koichi Sakaguchi et al. Medicine (Baltimore). 2019 Aug.

Abstract

Background: Osteoporosis is a major side effect of aromatase inhibitors (AIs), which are greatly effective in the treatment of breast cancer. However, there are no satisfactory measures against osteoporosis. In this multicenter, randomized, comparative study, we evaluate the efficacy of denosumab for preventing loss of bone mineral density (BMD) induced by adjuvant therapy with AI s in breast cancer patients with normal BMD.

Patients and methods: The bone loss-suppressing effect of denosumab will be comparatively evaluated in postmenopausal patients scheduled to receive letrozole or anastrozole as a postoperative endocrine therapy for stage I-IIIA hormone-sensitive breast cancer and a control group. Patients will be administered letrozole 2.5 mg or anastrozole 1 mg once a day, and the treatment will be continued for 5 years unless recurrence, secondary cancer, or unacceptable toxicity develops. Patients in the denosumab group will receive a subcutaneous injection of 60 mg of denosumab every 6 months. The primary endpoint is the rate of change in the lumbar spine (L1-L4) BMD, as determined by dual-energy X-ray absorptiometry (DXA), 12 months after the start of the injection. The secondary endpoints were ETHICS AND DISSEMINATION:: The protocol was approved by the institutional review boards of Kyoto Prefectural University of Medicine and all the participating faculties. Written informed consent was obtained from all patients before registration, in accordance with the Declaration of Helsinki. Results of the study will be disseminated via publications in peer-reviewed journals.

Trial registration: Clinical Trials.gov Identifier: NCT03324932, Japan Registry of Clinical Trial (jRCT): CRB5180001.

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Conflict of interest statement

This study was conducted as the 2016–2017 acupuncture study of the Japan Breast Cancer Society. There is no conflict of interest to be disclosed between this study and the Japan Breast Cancer Society. TT received Research grant from Chugai, Taiho and Daiichi Sankyo. ST received research grant from Daiichi Sankyo. IY has received a speaker fee from Chugai and JT. NN has received research funding to Tokai University from Novartis, Bristol-Myers Squibb, Chugai, Nihon Medi-Physics, MSD, Daiichi-Sankyo, honoraria, consultancy and speaker fees from AstraZeneca, Novartis, Eisai, and Pfizer, outside the submitted work. Other authors declare that they have no conflict of interest.

Figures

Figure 1
Figure 1
Trial Regimens. Patients are administered letrozole 2.5 mg or anastrozole 1 mg once a day, continued for 5 years. For the denosumab group, patients are administered denosumab subcutaneously at a dose of 60 mg every 6 months. The Primary endpoint is the rate of change of the lumbar spine (L1-L4) BMD by the DXA method 12 months after the start of the injection.
See this image and copyright information in PMC

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