CDK 4/6 inhibitors are associated with a high incidence of thrombotic events in women with breast cancer in real-world practice
© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd..
PURPOSE: Cyclin-dependent kinase (CDK) 4/6 inhibitors are integral treatment for advanced hormone receptor positive breast cancer; however, venous thromboembolic events (VTE) occurred in 1%-5% of clinical trial patients. Thrombosis rates in the real-world setting remain unclear. We aimed to define the rate of thromboembolic events, risk factors for thrombosis on CDK 4/6 inhibitors and evaluate the Khorana VTE risk score as a predictive tool for VTE in patients on CDK 4/6 therapy.
METHODS: Multicenter retrospective analysis of adult breast cancer patients prescribed palbociclib, ribociclib, or abemaciclib. The primary endpoint was thrombosis during treatment or within 30 days of CDK inhibitor discontinuation. Cox regression was used to model time-to-thrombosis, starting from a patient's initiation of CDK 4/6 therapy. The extended Kaplan-Meier method and Cox modeling were used to assess the effect of time-varying thrombosis status on overall survival.
RESULTS: Two hundred and sixty-six patients were included (89% on palbociclib, 14% on abemaciclib, 7% on ribociclib). Twenty-nine thrombotic events occurred in 26 (9.8%) women. Of these events, 72% were venous and 34% were arterial. The 1-year incidence of thrombosis was 10.4% overall, 10.9% on palbociclib, 8.3% on ribociclib, and 4.8% on abemaciclib. Hemoglobin less than 10 g/dL was a statistically significant predictor of thrombosis (HR 3.53, P: .014). Khorana score ranged from 0-3, with the majority between 0 and 1 and was not predictive of VTE. Thrombosis was associated with reduced overall survival (HR 1.28, P: .128, median 7.3 months) compared to not having a CDK-associated clot (median 35.7 months).
DISCUSSION: VTE in our analysis is higher than reported in clinical trials and arterial thrombosis comprised over one-third of events. The highest incidence was with palbociclib, followed by ribociclib. Khorana score did not predict VTE risk. Larger, real-world studies are needed. The role for prophylactic anticoagulation is yet to be defined in this patient population.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:106 |
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| Enthalten in: |
European journal of haematology - 106(2021), 5 vom: 01. Mai, Seite 634-642 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
West, Malinda T [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 03.12.2021 Date Revised 03.05.2022 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1111/ejh.13590 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM320884732 |
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| 100 | 1 | |a West, Malinda T |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a CDK 4/6 inhibitors are associated with a high incidence of thrombotic events in women with breast cancer in real-world practice |
| 264 | 1 | |c 2021 | |
| 336 | |a Text |b txt |2 rdacontent | ||
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| 500 | |a Date Completed 03.12.2021 | ||
| 500 | |a Date Revised 03.05.2022 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. | ||
| 520 | |a PURPOSE: Cyclin-dependent kinase (CDK) 4/6 inhibitors are integral treatment for advanced hormone receptor positive breast cancer; however, venous thromboembolic events (VTE) occurred in 1%-5% of clinical trial patients. Thrombosis rates in the real-world setting remain unclear. We aimed to define the rate of thromboembolic events, risk factors for thrombosis on CDK 4/6 inhibitors and evaluate the Khorana VTE risk score as a predictive tool for VTE in patients on CDK 4/6 therapy | ||
| 520 | |a METHODS: Multicenter retrospective analysis of adult breast cancer patients prescribed palbociclib, ribociclib, or abemaciclib. The primary endpoint was thrombosis during treatment or within 30 days of CDK inhibitor discontinuation. Cox regression was used to model time-to-thrombosis, starting from a patient's initiation of CDK 4/6 therapy. The extended Kaplan-Meier method and Cox modeling were used to assess the effect of time-varying thrombosis status on overall survival | ||
| 520 | |a RESULTS: Two hundred and sixty-six patients were included (89% on palbociclib, 14% on abemaciclib, 7% on ribociclib). Twenty-nine thrombotic events occurred in 26 (9.8%) women. Of these events, 72% were venous and 34% were arterial. The 1-year incidence of thrombosis was 10.4% overall, 10.9% on palbociclib, 8.3% on ribociclib, and 4.8% on abemaciclib. Hemoglobin less than 10 g/dL was a statistically significant predictor of thrombosis (HR 3.53, P: .014). Khorana score ranged from 0-3, with the majority between 0 and 1 and was not predictive of VTE. Thrombosis was associated with reduced overall survival (HR 1.28, P: .128, median 7.3 months) compared to not having a CDK-associated clot (median 35.7 months) | ||
| 520 | |a DISCUSSION: VTE in our analysis is higher than reported in clinical trials and arterial thrombosis comprised over one-third of events. The highest incidence was with palbociclib, followed by ribociclib. Khorana score did not predict VTE risk. Larger, real-world studies are needed. The role for prophylactic anticoagulation is yet to be defined in this patient population | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Multicenter Study | |
| 650 | 4 | |a CDK inhibitor | |
| 650 | 4 | |a arterial | |
| 650 | 4 | |a breast cancer | |
| 650 | 4 | |a thrombosis | |
| 650 | 4 | |a venous | |
| 650 | 7 | |a Protein Kinase Inhibitors |2 NLM | |
| 650 | 7 | |a CDK4 protein, human |2 NLM | |
| 650 | 7 | |a EC 2.7.11.22 |2 NLM | |
| 650 | 7 | |a CDK6 protein, human |2 NLM | |
| 650 | 7 | |a EC 2.7.11.22 |2 NLM | |
| 650 | 7 | |a Cyclin-Dependent Kinase 4 |2 NLM | |
| 650 | 7 | |a EC 2.7.11.22 |2 NLM | |
| 650 | 7 | |a Cyclin-Dependent Kinase 6 |2 NLM | |
| 650 | 7 | |a EC 2.7.11.22 |2 NLM | |
| 700 | 1 | |a Smith, Claire E |e verfasserin |4 aut | |
| 700 | 1 | |a Kaempf, Andy |e verfasserin |4 aut | |
| 700 | 1 | |a Kohs, Tia C L |e verfasserin |4 aut | |
| 700 | 1 | |a Amirsoltani, Ramin |e verfasserin |4 aut | |
| 700 | 1 | |a Ribkoff, Jessica |e verfasserin |4 aut | |
| 700 | 1 | |a Choung, Josh Lee |e verfasserin |4 aut | |
| 700 | 1 | |a Palumbo, Alison |e verfasserin |4 aut | |
| 700 | 1 | |a Mitri, Zahi |e verfasserin |4 aut | |
| 700 | 1 | |a Shatzel, Joseph J |e verfasserin |4 aut | |
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