Cardiac biomarkers and cardiovascular side effects are associated with a reduced mortality of oncological patients receiving BRAF/MEK-Inhibitor therapy

Introduction In recent years, the advent of targeted therapies has transformed the field of oncology, delivering improved treatment outcomes for patients with various cancer diagnoses. Notably, the combination of BRAF and MEK inhibitors has demonstrated remarkable efficacy in managing BRAF-mutated cancers, such as metastatic melanoma and certain forms of advanced non-small cell lung cancer. Despite their substantial clinical benefits, BRAF and MEK inhibitors have been linked to a range of cardiovascular complications, including myocardial dysfunction (characterized by altered left ventricular function or myocardial strain), arterial hypertension, and arrhythmias. To investigate these cardiovascular complications and their potential association with increased mortality, an observational study was conducted. Methods The inclusion criteria encompassed patients who had previously taken (n=12), were currently taking (n=32), or had planned intake (n=60) of BRAF/MEK inhibitors at the time of their initial presentation at the outpatient clinic in our city. A total of 104 patients (mean age 56.6 ± 14.2 years) were included, comprising 61 males (mean age 57.7 ± 14.4 years) and 43 females (mean age 62.4 ± 13.4 years). Results During therapy, 46.6% of patients experienced at least one cardiac symptom, such as dyspnea, angina pectoris, cardiac arrhythmias, or elevated levels of the cardiac biomarker NT-proBNP. Interestingly, in the overall cohort, patients who developed cardiac complications while receiving BRAF/MEK inhibitors exhibited a significantly reduced 2-year mortality rate (OR 0.37, p=0.024). Patients who presented with an elevated NYHA classification (≥II) at their initial visit (p < 0.001), as well as those with an age-adjusted increase in NT-proBNP levels (OR 9.08, p = 0.045), exhibited a significantly higher mortality rate during the study period. The occurrence of an increased NT-proBNP levels over time correlated significantly with a known coronary heart disease (OR 8,33, p=0,007), an increase of hs-cTnT levels over the Threshold of 14ng/l (OR 4.35, p=0,004) as well as diabetes (OR 3.29, p=0.047). Conclusion Cardial biomarkers such as NT-proBNP and hs-cTnT help to identify patients at risk. Cardio-oncological surveillance of these patients and an accurately timed treatment of cardiac complications could help to improve the overall prognosis of patients receiving BRAF/MEK-Inhibitor therapy.