Melanoma: dual BRAF/MEK inhibition tied to greater cardiovascular risk

  • Mincu RI & al.
  • JAMA Netw Open
  • 2 Aug 2019

  • curated by Brian Richardson, PhD
  • Univadis Clinical Summaries
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Takeaway

  • A meta-analysis ties dual BRAF+MEK inhibition to an excess risk for cardiovascular adverse events (CVAEs) vs BRAF inhibitors alone in patients with melanoma.

Why this matters

  • A recent meta-analysis showed survival benefit with dual BRAF/MEK inhibition, but risks and benefit should be carefully weighed.

Key results

  • Combination vs monotherapy was associated with increased risks for:
    • Pulmonary embolism (2.2% vs 0.4%; risk ratio [RR], 4.36; P=.02).
    • Decreased left ventricular ejection fraction (LVEF: 8.1% vs 2.0%; RR, 3.72; P<.001>
    • Arterial hypertension (19.5% vs 14.0%; RR, 1.49; P=.005).
  • Combination therapy was associated with increased risks for high-grade:
    • Decreased LVEF (2.1% vs 0.7%; RR, 2.79; P=.005).
    • Arterial hypertension (8.0% vs 5.1%; RR, 1.54, P=.005).
  • Patients with a mean age
  • Risk for pulmonary embolism was higher with a mean follow-up of >15 months (RR, 7.70; P=.02).

Study design

  • 5 randomized clinical trials involving 2317 patients with melanoma were included in the meta-analysis.
  • Funding: none disclosed.

Limitations

  • Treatment regimens were different in the included studies.

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