Cardiotoxicity in patients with metastatic melanoma treated with BRAF/MEK inhibitors: a real-world analysis of incidence, risk factors, and reversibility
Background: BRAF/MEK inhibitors (BRAFi/MEKi) improve outcome in patients with BRAF-mutated metastatic melanoma but are associated with cardiotoxicity, leading to a decline in left ventricular ejection fraction (LVEF). This study aimed to evaluate the incidence, timeline, risk factors, and reversibil...
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Medical Journals Sweden
2025-04-01
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| Series: | Acta Oncologica |
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| Online Access: | https://medicaljournalssweden.se/actaoncologica/article/view/42567 |
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| author | Jonas K. Oddershede Ida K. Meklenborg Lars Bastholt Louise M. Guldbrandt Henrik Schmidt Rasmus B. Friis |
| author_facet | Jonas K. Oddershede Ida K. Meklenborg Lars Bastholt Louise M. Guldbrandt Henrik Schmidt Rasmus B. Friis |
| author_sort | Jonas K. Oddershede |
| collection | DOAJ |
| description | Background: BRAF/MEK inhibitors (BRAFi/MEKi) improve outcome in patients with BRAF-mutated metastatic melanoma but are associated with cardiotoxicity, leading to a decline in left ventricular ejection fraction (LVEF). This study aimed to evaluate the incidence, timeline, risk factors, and reversibility of BRAFi/MEKi-induced cardiotoxicity in a real-world setting.
Patients/materials and methods: Patients with metastatic melanoma (n = 170) treated with Encorafenib/Binimetinib, Vemurafenib/Cobimetinib, or Dabrafenib/Trametinib at Aarhus and Odense University Hospital, Denmark, from 2015 to 2023 were included. Cardiac function was assessed at baseline and every 3 months during treatment with either echocardiograms or multigated acquisition scans. Cardiotoxicity was defined as a reduction of LVEF by ≥10 percentage points (pp) to an LVEF < 50% (Major cardiotoxicity) or a reduction of LVEF by ≥15 pp but remaining > 50% (Minor cardiotoxicity).
Results: Cardiotoxicity occurred in 21% of patients, with 14% experiencing major cardiotoxicity. The mean time to LVEF decline was 187 days, with 92% of major cardiotoxicity cases occurring within the first year. Cardiotoxicity was reversible in 79% of patients following dose reduction, treatment pauses, heart failure therapy, or continued treatment with monitoring. Baseline atrial fibrillation (odds ratio 13.67, p = 0.008) was identified as a risk factor for major cardiotoxicity.
Interpretation: BRAFi/MEKi-induced cardiotoxicity is a significant but manageable complication, often reversible with timely interventions. Routine LVEF monitoring is recommended. The majority (92%) of major cardiac events were diagnosed within the first year of treatment, which might warrant a discontinuation of routine LVEF monitoring after 1 year of BRAFi/MEKi treatment.
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| format | Article |
| id | doaj-art-079082ec94db480bbf21b58c6ae51dab |
| institution | OA Journals |
| issn | 1651-226X |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Medical Journals Sweden |
| record_format | Article |
| series | Acta Oncologica |
| spelling | doaj-art-079082ec94db480bbf21b58c6ae51dab2025-08-20T02:16:06ZengMedical Journals SwedenActa Oncologica1651-226X2025-04-016410.2340/1651-226X.2025.42567Cardiotoxicity in patients with metastatic melanoma treated with BRAF/MEK inhibitors: a real-world analysis of incidence, risk factors, and reversibilityJonas K. Oddershede0https://orcid.org/0009-0006-2680-2361Ida K. Meklenborg1https://orcid.org/0009-0000-5343-4898Lars Bastholt2https://orcid.org/0000-0001-5478-9826Louise M. Guldbrandt3https://orcid.org/0009-0001-7452-6684Henrik Schmidt4https://orcid.org/0000-0002-4063-3561Rasmus B. Friis5https://orcid.org/0000-0002-0564-146XDepartment of Oncology, Aarhus University Hospital, Aarhus, DenmarkDepartment of Oncology, Odense University Hospital, Odense, DenmarkDepartment of Oncology, Odense University Hospital, Odense, DenmarkDepartment of Oncology, Aarhus University Hospital, Aarhus, DenmarkDepartment of Oncology, Aarhus University Hospital, Aarhus, DenmarkDepartment of Oncology, Aarhus University Hospital, Aarhus, DenmarkBackground: BRAF/MEK inhibitors (BRAFi/MEKi) improve outcome in patients with BRAF-mutated metastatic melanoma but are associated with cardiotoxicity, leading to a decline in left ventricular ejection fraction (LVEF). This study aimed to evaluate the incidence, timeline, risk factors, and reversibility of BRAFi/MEKi-induced cardiotoxicity in a real-world setting. Patients/materials and methods: Patients with metastatic melanoma (n = 170) treated with Encorafenib/Binimetinib, Vemurafenib/Cobimetinib, or Dabrafenib/Trametinib at Aarhus and Odense University Hospital, Denmark, from 2015 to 2023 were included. Cardiac function was assessed at baseline and every 3 months during treatment with either echocardiograms or multigated acquisition scans. Cardiotoxicity was defined as a reduction of LVEF by ≥10 percentage points (pp) to an LVEF < 50% (Major cardiotoxicity) or a reduction of LVEF by ≥15 pp but remaining > 50% (Minor cardiotoxicity). Results: Cardiotoxicity occurred in 21% of patients, with 14% experiencing major cardiotoxicity. The mean time to LVEF decline was 187 days, with 92% of major cardiotoxicity cases occurring within the first year. Cardiotoxicity was reversible in 79% of patients following dose reduction, treatment pauses, heart failure therapy, or continued treatment with monitoring. Baseline atrial fibrillation (odds ratio 13.67, p = 0.008) was identified as a risk factor for major cardiotoxicity. Interpretation: BRAFi/MEKi-induced cardiotoxicity is a significant but manageable complication, often reversible with timely interventions. Routine LVEF monitoring is recommended. The majority (92%) of major cardiac events were diagnosed within the first year of treatment, which might warrant a discontinuation of routine LVEF monitoring after 1 year of BRAFi/MEKi treatment. https://medicaljournalssweden.se/actaoncologica/article/view/42567BRAF/MEK inhibitioncardiotoxicitymalignant melanomaechocardiographymultigated acquisition scanoncocardiology |
| spellingShingle | Jonas K. Oddershede Ida K. Meklenborg Lars Bastholt Louise M. Guldbrandt Henrik Schmidt Rasmus B. Friis Cardiotoxicity in patients with metastatic melanoma treated with BRAF/MEK inhibitors: a real-world analysis of incidence, risk factors, and reversibility Acta Oncologica BRAF/MEK inhibition cardiotoxicity malignant melanoma echocardiography multigated acquisition scan oncocardiology |
| title | Cardiotoxicity in patients with metastatic melanoma treated with BRAF/MEK inhibitors: a real-world analysis of incidence, risk factors, and reversibility |
| title_full | Cardiotoxicity in patients with metastatic melanoma treated with BRAF/MEK inhibitors: a real-world analysis of incidence, risk factors, and reversibility |
| title_fullStr | Cardiotoxicity in patients with metastatic melanoma treated with BRAF/MEK inhibitors: a real-world analysis of incidence, risk factors, and reversibility |
| title_full_unstemmed | Cardiotoxicity in patients with metastatic melanoma treated with BRAF/MEK inhibitors: a real-world analysis of incidence, risk factors, and reversibility |
| title_short | Cardiotoxicity in patients with metastatic melanoma treated with BRAF/MEK inhibitors: a real-world analysis of incidence, risk factors, and reversibility |
| title_sort | cardiotoxicity in patients with metastatic melanoma treated with braf mek inhibitors a real world analysis of incidence risk factors and reversibility |
| topic | BRAF/MEK inhibition cardiotoxicity malignant melanoma echocardiography multigated acquisition scan oncocardiology |
| url | https://medicaljournalssweden.se/actaoncologica/article/view/42567 |
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