The findings of new research raise concerns that side effects of Zelboraf, Cotellic and other similar drugs used to treat melanoma, may increase the risk of serious heart problems when used in combination.
German researchers report that two classes of melanoma medication, BRAF and MEK inhibitors, more than quadrupled the risk of pulmonary embolism, nearly quadrupled the risk of left ventricular ejection fraction, and significantly increased the risk of arterial hypertension when used together.
The findings were published last week in the medical journal JAMA Network Open, raising serious concerns for the use of the medications to treat BRAF-mutated melanoma; which is a form of skin cancer that can be fatal.
In November 2015, the FDA approved the MEK inhibitor drug Cotellic (cobimetinib) for use in combination with the BRAF inhibitor Zelboraf (vemurafenib) for the treatment of advanced melanoma.
In this latest study, researchers sought to see whether the combination of medications was linked with an increased risk cardiovascular adverse events (CVAEs) when compared to the use of Zelboraf or other BRAF inhibitor momotherapies alone.
Researchers looked at data on five randomized clinical trials involving 2,317 patients with melanoma. According to the findings, combination therapy increased the risk of pulmonary embolism more than four-fold, the risk of a decrease in left ventricular ejection fraction almost as much, and increased arterial hypertension risks by nearly 50% when compared with monotherapy. It did not increase the risk of heart attacks, atrial fibrillation or QTc interval prolongation, however.
“Therapy with BRAF and MEK inhibitors was associated with a higher risk of CVAEs compared with BRAF inhibitor monotherapy,” the researchers concluded. “The findings may help to balance between beneficial melanoma treatment and cardiovascular morbidity and mortality.”
Last year, clinical trials combining Cotellic and Tecentriq were halted for the treatment of colorectal cancer due to a higher-than-expected rate of deaths. There were four deaths during the trials. Two of the deaths resulted from the continued progression of colorectal cancer, and the third death came from cardiogenic shock. A fourth death was reportedly unrelated to the study.
Skin cancer cases in the United States have increased significantly over the past decade, with the number of skin cancer cases in the U.S. reaching more than 260,000 in 2015, costing the U.S. healthcare system hundreds of millions of dollars in related medical costs. Melanoma is the deadliest form of skin cancer.
According to a melanoma diagnosis study published in the Journal of the American Medical Association (JAMA), researchers estimated roughly 80,000 Americans were diagnosed with melanoma in 2016, resulting in at least 10,000 fatalities.