Cardiotoxicity in patients with metastatic melanoma treated with BRAF/MEK inhibitors: a real-world analysis of incidence, risk factors, and reversibility

被引:0
作者
Oddershede, Jonas K. [1 ]
Meklenborg, Ida K. [2 ]
Bastholt, Lars [2 ]
Guldbrandt, Louise M. [1 ]
Schmidt, Henrik [1 ]
Friis, Rasmus B. [1 ]
机构
[1] Aarhus Univ Hosp, Dept Oncol, Aarhus, Denmark
[2] Odense Univ Hosp, Dept Oncol, Odense, Denmark
关键词
BRAF/MEK inhibition; cardiotoxicity; malignant melanoma; echocardiography; multigated acquisition scan; oncocardiology; antineoplastic therapy; CANCER-THERAPY; MEK INHIBITION; HEART-RATE; DABRAFENIB; SURVIVAL; PHASE-3; SAFETY; VEMURAFENIB; TRAMETINIB; EFFICACY;
D O I
10.2340/1651-226X.2025.42567
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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) ora reduction of LVEF by >= 15 pp but remaining > 50%(Minorcardiotoxicity). 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.
引用
收藏
页码:507 / 515
页数:9
相关论文
共 35 条
[21]   Cancer Therapy-Induced Cardiac Toxicity in Early Breast Cancer Addressing the Unresolved Issues [J].
Khouri, Michel G. ;
Douglas, Pamela S. ;
Mackey, John R. ;
Martin, Miguel ;
Scott, Jessica M. ;
Scherrer-Crosbie, Marielle ;
Jones, Lee W. .
CIRCULATION, 2012, 126 (23) :2749-2763
[22]   High-throughput sequencing of the melanoma genome [J].
Kunz, Manfred ;
Dannemann, Michael ;
Kelso, Janet .
EXPERIMENTAL DERMATOLOGY, 2013, 22 (01) :10-17
[23]   BRAF, MEK and KIT inhibitors for melanoma: adverse events and their management [J].
Livingstone, Elisabeth ;
Zimmer, Lisa ;
Vaubel, Julia ;
Schadendorf, Dirk .
CHINESE CLINICAL ONCOLOGY, 2014, 3 (03)
[24]   Dabrafenib plus trametinib versus dabrafenib monotherapy in patients with metastatic BRAF V600E/K-mutant melanoma: long-term survival and safety analysis of a phase 3 study [J].
Long, G. V. ;
Flaherty, K. T. ;
Stroyakovskiy, D. ;
Gogas, H. ;
Levchenko, E. ;
de Braud, F. ;
Larkin, J. ;
Garbe, C. ;
Jouary, T. ;
Hauschild, A. ;
Chiarion-Sileni, V. ;
Lebbe, C. ;
Mandala, M. ;
Millward, M. ;
Arance, A. ;
Bondarenko, I. ;
Haanen, J. B. A. G. ;
Hansson, J. ;
Utikal, J. ;
Ferraresi, V. ;
Mohr, P. ;
Probachai, V. ;
Schadendorf, D. ;
Nathan, P. ;
Robert, C. ;
Ribas, A. ;
Davies, M. A. ;
Lane, S. R. ;
Legos, J. J. ;
Mookerjee, B. ;
Grob, J. -J. .
ANNALS OF ONCOLOGY, 2017, 28 (07) :1631-1639
[25]   Safety and efficacy of vemurafenib in BRAFV600E and BRAFV600K mutation-positive melanoma (BRIM-3): extended follow-up of a phase 3, randomised, open-label study [J].
McArthur, Grant A. ;
Chapman, Paul B. ;
Robert, Caroline ;
Larkin, James ;
Haanen, John B. ;
Dummer, Reinhard ;
Ribas, Antoni ;
Hogg, David ;
Hamid, Omid ;
Ascierto, Paolo A. ;
Garbe, Claus ;
Testori, Alessandro ;
Maio, Michele ;
Lorigan, Paul ;
Lebbe, Celeste ;
Jouary, Thomas ;
Schadendorf, Dirk ;
O'Day, Stephen J. ;
Kirkwood, John M. ;
Eggermont, Alexander M. ;
Dreno, Brigitte ;
Sosman, Jefferey A. ;
Flaherty, Keith T. ;
Yin, Ming ;
Caro, Ivor ;
Cheng, Suzanne ;
Trunzer, Kerstin ;
Hauschild, Axel .
LANCET ONCOLOGY, 2014, 15 (03) :323-332
[26]   Cardiovascular Adverse Events Associated With BRAF and MEK Inhibitors A Systematic Review and Meta-analysis [J].
Mincu, Raluca I. ;
Mahabadi, Amir A. ;
Michel, Lars ;
Mrotzek, Simone M. ;
Schadendorf, Dirk ;
Rassaf, Tienush ;
Totzeck, Matthias .
JAMA NETWORK OPEN, 2019, 2 (08) :E198890
[27]   Cardiotoxicity in metastatic melanoma patients treated with BRAF and MEK inhibitors in a real-world setting [J].
Pedersen, Sidsel ;
Larsen, Kirstine Ostenfeld ;
Christensen, Alex Horby ;
Svane, Inge Marie ;
Zerahn, Bo ;
Ellebaek, Eva .
ACTA ONCOLOGICA, 2022, 61 (01) :45-51
[28]   Cancer Therapy-Related Cardiac Dysfunction: An Overview for the Clinician [J].
Perez, Irving E. ;
Alam, Sara Taveras ;
Hernandez, Gabriel A. ;
Sancassani, Rhea .
CLINICAL MEDICINE INSIGHTS-CARDIOLOGY, 2019, 13
[29]  
Plana JC, 2014, J AM SOC ECHOCARDIOG, V27, P911, DOI [10.1093/ehjci/jeu192, 10.1016/j.echo.2014.07.012]
[30]   LVEF by Multigated Acquisition Scan Compared to Other Imaging Modalities in Cardio-Oncology: a Systematic Review [J].
Printezi, Markella, I ;
Yousif, Laura I. E. ;
Kamphuis, Janine A. M. ;
van Laake, Linda W. ;
Cramer, Maarten J. ;
Hobbelink, Monique G. G. ;
Asselbergs, Folkert W. ;
Teske, Arco J. .
CURRENT HEART FAILURE REPORTS, 2022, 19 (03) :136-145