Association between CDK4/6 inhibitors and drug-related osteonecrosis of the jaw : A pharmacoepidemiological study using the FDA Adverse Events Reporting System
© 2024 UICC..
The most common toxicities associated with cyclin-dependent kinase (CDK) 4/6 inhibitor therapy include decreased leukopenia and neutropenia due to the inhibition of CDK6 of leukocyte and neutrophil precursors in bone marrow. These hematological toxicities are more commonly observed with palbociclib administration than with abemaciclib administration, which is approximately 13 times more selective against CDK4 than CDK6. Thus, even though both successfully inhibit CDK4/6, the side effects of palbociclib and abemaciclib differ due to differences in selectivity. Recent reports have suggested an association between palbociclib and medication-related osteonecrosis of the jaw; however, reports on this association are inconsistent. This study investigated the potential association of palbociclib and abemaciclib with MRONJ using the FAERS. Signals of "Osteonecrosis of jaw" were detected only in females using palbociclib (cROR025: 2.08). Other signals detected included stomatitis-related adverse events with abemaciclib and intraoral soft tissue damage and infection with palbociclib. As previous exploratory studies have reported MRONJ signals for bisphosphonates and denosumab, we calculated the aROR for palbociclib-induced osteonecrosis of the jaw using concomitant bisphosphonates and denosumab as covariates. A signal was detected even after adjusting for sex, age, and concomitant medications as covariates (aROR0025: 5.74). A proper understanding of the differences in CDK selectivity is necessary for the appropriate use of CDK4/6 inhibitors. To the best of our knowledge, this is the first report on CDK4/6 inhibitors and drug-related osteonecrosis of the jaw. We believe that these results will offer new insights into adverse events related to the use of CDK4/6 inhibitors, and may aid in the proper use of CDK4/6 inhibitors.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - year:2024 |
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| Enthalten in: |
International journal of cancer - (2024) vom: 15. Apr. |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Go, Makiko [VerfasserIn] |
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| Links: |
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| Themen: |
Abemaciclib |
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| Anmerkungen: |
Date Revised 15.04.2024 published: Print-Electronic Citation Status Publisher |
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| doi: |
10.1002/ijc.34962 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM371085225 |
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| 245 | 1 | 0 | |a Association between CDK4/6 inhibitors and drug-related osteonecrosis of the jaw |b A pharmacoepidemiological study using the FDA Adverse Events Reporting System |
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| 520 | |a The most common toxicities associated with cyclin-dependent kinase (CDK) 4/6 inhibitor therapy include decreased leukopenia and neutropenia due to the inhibition of CDK6 of leukocyte and neutrophil precursors in bone marrow. These hematological toxicities are more commonly observed with palbociclib administration than with abemaciclib administration, which is approximately 13 times more selective against CDK4 than CDK6. Thus, even though both successfully inhibit CDK4/6, the side effects of palbociclib and abemaciclib differ due to differences in selectivity. Recent reports have suggested an association between palbociclib and medication-related osteonecrosis of the jaw; however, reports on this association are inconsistent. This study investigated the potential association of palbociclib and abemaciclib with MRONJ using the FAERS. Signals of "Osteonecrosis of jaw" were detected only in females using palbociclib (cROR025: 2.08). Other signals detected included stomatitis-related adverse events with abemaciclib and intraoral soft tissue damage and infection with palbociclib. As previous exploratory studies have reported MRONJ signals for bisphosphonates and denosumab, we calculated the aROR for palbociclib-induced osteonecrosis of the jaw using concomitant bisphosphonates and denosumab as covariates. A signal was detected even after adjusting for sex, age, and concomitant medications as covariates (aROR0025: 5.74). A proper understanding of the differences in CDK selectivity is necessary for the appropriate use of CDK4/6 inhibitors. To the best of our knowledge, this is the first report on CDK4/6 inhibitors and drug-related osteonecrosis of the jaw. We believe that these results will offer new insights into adverse events related to the use of CDK4/6 inhibitors, and may aid in the proper use of CDK4/6 inhibitors | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a CDK4/6 inhibitor | |
| 650 | 4 | |a FAERS | |
| 650 | 4 | |a abemaciclib | |
| 650 | 4 | |a osteonecrosis of the jaw | |
| 650 | 4 | |a palbociclib | |
| 700 | 1 | |a Noguchi, Yoshihiro |e verfasserin |4 aut | |
| 700 | 1 | |a Masuda, Rikuto |e verfasserin |4 aut | |
| 700 | 1 | |a Asano, Hiroki |e verfasserin |4 aut | |
| 700 | 1 | |a Kimura, Michio |e verfasserin |4 aut | |
| 700 | 1 | |a Usami, Eiseki |e verfasserin |4 aut | |
| 700 | 1 | |a Yoshimura, Tomoaki |e verfasserin |4 aut | |
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