Cardiovascular adverse events of BRAF and/or MEK inhibitors in cancer patients: a systematic review and meta-analysis of placebo randomized- controlled trials

Abstract : Background: cardiovascular adverse events (CVAE) risk of BRAF and mitogen-activated extracellular signalregulated kinase (MEK) inhibitors are not fully characterized. Objectives: we aimed to evaluate the incidence of CVAE in BRAF and/or MEK inhibitors used in monotherapy and in combination therapy. Methods: Medline, Embase and the Cochrane Library databases were searched from database inception through September 18, 2018 for efficacy randomized placebo-controlled trials (RPCTs) of BRAF and/or MEK inhibitors with CVAE data collection. We performed a systematic review and meta-analysis to compute random-effect summary oddsratios (OR) with 95% confidence intervals (CI) of CVAE. The primary outcomes were hypertension, ejection fraction decrease and peripheral oedema occurrences. PROSPERO registration number: CRD42018094729. Results: we included 11 RPCTs, with a total number of 1,722 patients in monotherapy trials and 953 patients in combination therapy trials. In monotherapy trials, there was a significantly higher incidence of ejection fraction decrease (OR 3.36, 95%CI 1.63-6.94, p=0.001, I²=5%) and peripheral oedema (OR 2.64, 95%CI 2.03-3.42, p<0.001, I²=50%) but not hypertension (OR 1.81, 95%CI 0.97-3.35, p=0.06, I²=50%) in BRAF or MEK inhibitor groups versus placebo. BRAF or MEK inhibitor groups had a significantly higher incidence of syncope versus placebo and a significantly lower incidence of phlebitis, and atrial flutter. In combination therapy trials, there was an additional higher incidence of ejection fraction decrease in combination groups versus monotherapy plus placebo. Conclusion: BRAF or MEK inhibitors in cancer patients are associated with a higher incidence of ejection fraction decrease and peripheral oedema with an additional higher incidence of ejection fraction decrease in combination therapies.
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Charles Dolladille. Cardiovascular adverse events of BRAF and/or MEK inhibitors in cancer patients: a systematic review and meta-analysis of placebo randomized- controlled trials. Human health and pathology. 2018. ⟨dumas-02104055⟩

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