Left ventricular ejection fraction decrease related to BRAF and/or MEK inhibitors in metastatic melanoma patients: A retrospective analysis
Abstract BRAF and MEKis have revolutionized the management of BRAFV600‐mutated melanoma patients. Left ventricular ejection fraction decrease (LVEF‐D) related to these treatments has not been thoroughly evaluated to date. The main objective of this study was to describe characteristics of LVEF‐D in...
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Wiley
2020-04-01
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| Series: | Cancer Medicine |
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| Online Access: | https://doi.org/10.1002/cam4.2922 |
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| author | Mathilde Berger Mona Amini‐Adlé Delphine Maucort‐Boulch Philip Robinson Luc Thomas Stéphane Dalle Pierre‐Yves Courand |
| author_facet | Mathilde Berger Mona Amini‐Adlé Delphine Maucort‐Boulch Philip Robinson Luc Thomas Stéphane Dalle Pierre‐Yves Courand |
| author_sort | Mathilde Berger |
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| description | Abstract BRAF and MEKis have revolutionized the management of BRAFV600‐mutated melanoma patients. Left ventricular ejection fraction decrease (LVEF‐D) related to these treatments has not been thoroughly evaluated to date. The main objective of this study was to describe characteristics of LVEF‐D in melanoma patients treated with BRAF and/or MEKis. Metastatic melanoma patients treated with BRAF and/or MEKis between March 1, 2012 and May 18, 2018 were included retrospectively (Lyon Sud University Hospital, Hospices Civils de Lyon). LVEF‐D was defined as a reduction in LVEF ≥10% from baseline to a value <55%; normalization was defined as a value ≥55%. Among the 88 patients included, 12 (13.6%) experienced a LVEF‐D, including 10 grade 2 and 2 grade 3. The median onset of which was 11 months (IQR [3‐21]). No patient previously treated with beta‐blockers (n = 12) experienced a LVEF‐D. Analysis of laboratory parameters, electrocardiogram, and transthoracic echocardiography during the follow‐up did not find any predictive marker of LVEF‐D. All patients who benefited from a specific treatment of LVEF‐D had a normalization of LVEF at the end of follow‐up. LVEF recovery was significantly better for patients treated with angiotensin converting enzyme inhibitors and beta‐blockers than those who did not (P = .019). Ophthalmological adverse events were significantly more frequent in patients who experienced a LVEF‐D (P = .006) and the latter did not influence overall‐survival (P = .117) or progression‐free‐survival (P = .297). LVEF‐D is a common and easily manageable adverse event due to BRAF and MEKis. Its association with ocular toxicity suggests a close ophthalmological monitoring when LVEF‐D occurs. |
| format | Article |
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| institution | Kabale University |
| issn | 2045-7634 |
| language | English |
| publishDate | 2020-04-01 |
| publisher | Wiley |
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| series | Cancer Medicine |
| spelling | doaj-art-ecce891d2f4d40d98a56ce56d1a2b7c12025-08-20T03:44:11ZengWileyCancer Medicine2045-76342020-04-01982611262010.1002/cam4.2922Left ventricular ejection fraction decrease related to BRAF and/or MEK inhibitors in metastatic melanoma patients: A retrospective analysisMathilde Berger0Mona Amini‐Adlé1Delphine Maucort‐Boulch2Philip Robinson3Luc Thomas4Stéphane Dalle5Pierre‐Yves Courand6Service de dermatologie Centre Hospitalier Lyon Sud Hospices Civils de Lyon Pierre‐Bénite FranceService de dermatologie Centre Hospitalier Lyon Sud Hospices Civils de Lyon Pierre‐Bénite FranceService de Biostatistiques Hospices Civils de Lyon Université Lyon 1 Lyon FranceDirection de la Recherche Clinique et de l’Innovation Hospices Civils de Lyon Lyon FranceService de dermatologie Centre Hospitalier Lyon Sud Hospices Civils de Lyon Pierre‐Bénite FranceService de dermatologie Centre Hospitalier Lyon Sud Hospices Civils de Lyon Pierre‐Bénite FranceHospices Civils de Lyon Service de cardiologie Hôpital de la Croix‐Rousse et Centre Hospitalier Lyon Sud Lyon FranceAbstract BRAF and MEKis have revolutionized the management of BRAFV600‐mutated melanoma patients. Left ventricular ejection fraction decrease (LVEF‐D) related to these treatments has not been thoroughly evaluated to date. The main objective of this study was to describe characteristics of LVEF‐D in melanoma patients treated with BRAF and/or MEKis. Metastatic melanoma patients treated with BRAF and/or MEKis between March 1, 2012 and May 18, 2018 were included retrospectively (Lyon Sud University Hospital, Hospices Civils de Lyon). LVEF‐D was defined as a reduction in LVEF ≥10% from baseline to a value <55%; normalization was defined as a value ≥55%. Among the 88 patients included, 12 (13.6%) experienced a LVEF‐D, including 10 grade 2 and 2 grade 3. The median onset of which was 11 months (IQR [3‐21]). No patient previously treated with beta‐blockers (n = 12) experienced a LVEF‐D. Analysis of laboratory parameters, electrocardiogram, and transthoracic echocardiography during the follow‐up did not find any predictive marker of LVEF‐D. All patients who benefited from a specific treatment of LVEF‐D had a normalization of LVEF at the end of follow‐up. LVEF recovery was significantly better for patients treated with angiotensin converting enzyme inhibitors and beta‐blockers than those who did not (P = .019). Ophthalmological adverse events were significantly more frequent in patients who experienced a LVEF‐D (P = .006) and the latter did not influence overall‐survival (P = .117) or progression‐free‐survival (P = .297). LVEF‐D is a common and easily manageable adverse event due to BRAF and MEKis. Its association with ocular toxicity suggests a close ophthalmological monitoring when LVEF‐D occurs.https://doi.org/10.1002/cam4.2922adverse eventsBRAF inhibitorcardiac toxicityheart failureleft ventricular ejection fractionleft ventricular systolic dysfunction |
| spellingShingle | Mathilde Berger Mona Amini‐Adlé Delphine Maucort‐Boulch Philip Robinson Luc Thomas Stéphane Dalle Pierre‐Yves Courand Left ventricular ejection fraction decrease related to BRAF and/or MEK inhibitors in metastatic melanoma patients: A retrospective analysis Cancer Medicine adverse events BRAF inhibitor cardiac toxicity heart failure left ventricular ejection fraction left ventricular systolic dysfunction |
| title | Left ventricular ejection fraction decrease related to BRAF and/or MEK inhibitors in metastatic melanoma patients: A retrospective analysis |
| title_full | Left ventricular ejection fraction decrease related to BRAF and/or MEK inhibitors in metastatic melanoma patients: A retrospective analysis |
| title_fullStr | Left ventricular ejection fraction decrease related to BRAF and/or MEK inhibitors in metastatic melanoma patients: A retrospective analysis |
| title_full_unstemmed | Left ventricular ejection fraction decrease related to BRAF and/or MEK inhibitors in metastatic melanoma patients: A retrospective analysis |
| title_short | Left ventricular ejection fraction decrease related to BRAF and/or MEK inhibitors in metastatic melanoma patients: A retrospective analysis |
| title_sort | left ventricular ejection fraction decrease related to braf and or mek inhibitors in metastatic melanoma patients a retrospective analysis |
| topic | adverse events BRAF inhibitor cardiac toxicity heart failure left ventricular ejection fraction left ventricular systolic dysfunction |
| url | https://doi.org/10.1002/cam4.2922 |
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