Long-term use of denosumab and its association with skeletal-related events and osteonecrosis of the jaw
Abstract Denosumab, an inhibitor of receptor activator of nuclear factor kappa-B ligand, reduces skeletal-related events (SREs) and is approved for solid tumors with bone metastases. We studied long-term denosumab efficacy and safety because real-world data is scarce. This single-arm, single-center...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2023-05-01
|
| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-023-35308-z |
| _version_ | 1797818032273227776 |
|---|---|
| author | Pei-An Fu Chin-Yao Shen Shuen‑Ru Yang Chun-Hui Lee Hui-Wen Chen Edward Chia-Cheng Lai Wei-Pang Chung |
| author_facet | Pei-An Fu Chin-Yao Shen Shuen‑Ru Yang Chun-Hui Lee Hui-Wen Chen Edward Chia-Cheng Lai Wei-Pang Chung |
| author_sort | Pei-An Fu |
| collection | DOAJ |
| description | Abstract Denosumab, an inhibitor of receptor activator of nuclear factor kappa-B ligand, reduces skeletal-related events (SREs) and is approved for solid tumors with bone metastases. We studied long-term denosumab efficacy and safety because real-world data is scarce. This single-arm, single-center retrospective study included denosumab-treated breast cancer patients with bone metastases. Kaplan–Meier survival curves assessed exposure, SREs, osteonecrosis of the jaw (ONJ), and death. 132 patients were enrolled. The median denosumab exposure was 28.3 months (range 1.0–84.9). In the first year, 11.1% experienced SREs. This increased to 18.6% in the second, 21% in the third, and 35.1% in the fourth year and beyond. The median time to first on-study SRE has not been reached. 10 denosumab users (7.6%) developed ONJ. ONJ incidence was 0.9% in the first year, 6.2% in the second, 13.6% in the third, and 16.2% in subsequent years. The median time to first on-study ONJ has not been reached yet. Seven patients resumed denosumab after careful management of ONJ. Our data suggest that long-term treatment with denosumab may further prevent or postpone SREs at the cost of an increased risk of ONJ. The majority of patients who resumed denosumab did not experience a recurrence of ONJ. |
| first_indexed | 2024-03-13T09:02:15Z |
| format | Article |
| id | doaj.art-02fe4642992d4c29af5e341e538fa124 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-03-13T09:02:15Z |
| publishDate | 2023-05-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-02fe4642992d4c29af5e341e538fa1242023-05-28T11:14:25ZengNature PortfolioScientific Reports2045-23222023-05-011311810.1038/s41598-023-35308-zLong-term use of denosumab and its association with skeletal-related events and osteonecrosis of the jawPei-An Fu0Chin-Yao Shen1Shuen‑Ru Yang2Chun-Hui Lee3Hui-Wen Chen4Edward Chia-Cheng Lai5Wei-Pang Chung6Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung UniversitySchool of Pharmacy, Institute of Clinical Pharmacy and Pharmaceutical Sciences, College of Medicine, National Cheng Kung UniversityDepartment of Oncology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung UniversityDepartment of Oncology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung UniversityDepartment of Pathology, College of Medicine, National Cheng Kung University Hospital, National Cheng Kung UniversitySchool of Pharmacy, Institute of Clinical Pharmacy and Pharmaceutical Sciences, College of Medicine, National Cheng Kung UniversityDepartment of Oncology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung UniversityAbstract Denosumab, an inhibitor of receptor activator of nuclear factor kappa-B ligand, reduces skeletal-related events (SREs) and is approved for solid tumors with bone metastases. We studied long-term denosumab efficacy and safety because real-world data is scarce. This single-arm, single-center retrospective study included denosumab-treated breast cancer patients with bone metastases. Kaplan–Meier survival curves assessed exposure, SREs, osteonecrosis of the jaw (ONJ), and death. 132 patients were enrolled. The median denosumab exposure was 28.3 months (range 1.0–84.9). In the first year, 11.1% experienced SREs. This increased to 18.6% in the second, 21% in the third, and 35.1% in the fourth year and beyond. The median time to first on-study SRE has not been reached. 10 denosumab users (7.6%) developed ONJ. ONJ incidence was 0.9% in the first year, 6.2% in the second, 13.6% in the third, and 16.2% in subsequent years. The median time to first on-study ONJ has not been reached yet. Seven patients resumed denosumab after careful management of ONJ. Our data suggest that long-term treatment with denosumab may further prevent or postpone SREs at the cost of an increased risk of ONJ. The majority of patients who resumed denosumab did not experience a recurrence of ONJ.https://doi.org/10.1038/s41598-023-35308-z |
| spellingShingle | Pei-An Fu Chin-Yao Shen Shuen‑Ru Yang Chun-Hui Lee Hui-Wen Chen Edward Chia-Cheng Lai Wei-Pang Chung Long-term use of denosumab and its association with skeletal-related events and osteonecrosis of the jaw Scientific Reports |
| title | Long-term use of denosumab and its association with skeletal-related events and osteonecrosis of the jaw |
| title_full | Long-term use of denosumab and its association with skeletal-related events and osteonecrosis of the jaw |
| title_fullStr | Long-term use of denosumab and its association with skeletal-related events and osteonecrosis of the jaw |
| title_full_unstemmed | Long-term use of denosumab and its association with skeletal-related events and osteonecrosis of the jaw |
| title_short | Long-term use of denosumab and its association with skeletal-related events and osteonecrosis of the jaw |
| title_sort | long term use of denosumab and its association with skeletal related events and osteonecrosis of the jaw |
| url | https://doi.org/10.1038/s41598-023-35308-z |
| work_keys_str_mv | AT peianfu longtermuseofdenosumabanditsassociationwithskeletalrelatedeventsandosteonecrosisofthejaw AT chinyaoshen longtermuseofdenosumabanditsassociationwithskeletalrelatedeventsandosteonecrosisofthejaw AT shuenruyang longtermuseofdenosumabanditsassociationwithskeletalrelatedeventsandosteonecrosisofthejaw AT chunhuilee longtermuseofdenosumabanditsassociationwithskeletalrelatedeventsandosteonecrosisofthejaw AT huiwenchen longtermuseofdenosumabanditsassociationwithskeletalrelatedeventsandosteonecrosisofthejaw AT edwardchiachenglai longtermuseofdenosumabanditsassociationwithskeletalrelatedeventsandosteonecrosisofthejaw AT weipangchung longtermuseofdenosumabanditsassociationwithskeletalrelatedeventsandosteonecrosisofthejaw |