Tagrisso, Lazcluze Side Effects Increase Heart Risks: Study

New generation EGFR inhibitor cancer drugs have been linked to reports of heart attacks, strokes, hypertension, blood clots, heart failure and other side effects.

Chinese researchers warn that patients taking new cancer drugs like Tagrisso and Lazcluze face a much higher risk of heart problems than those prescribed first generation versions like Tarceva.

The medications are part of a class of medications known as epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors, which are designed to slow cell growth in certain cancers, such as non-small cell lung cancer.

While the drugs are particularly effective against tumors with genetic mutations that make them resistant to older treatments, new findings published late last month in the medical journal The BMJ indicate that patients who used Tagrisso and Lazcluze faced a threefold risk of arrhythmias, heart failure and stroke compared to those taking older drugs.

Tagrisso was developed by AstraZeneca and approved by the U.S. Food and Drug Administration (FDA) in 2015, becoming one of the leading third-generation EGFR inhibitors. However, research has linked Tagrisso to increased cardiovascular risks, with earlier studies suggesting patients may face up to a fourfold higher risk of heart disease, heart attacks and heart failure.

In addition, a 2022 case report from Canadian doctors warned that Tagrisso side effects may also trigger severe skin toxicities, including psoriasis and toxic epidermal necrolysis (TEN), a rare but potentially fatal condition.

In this new study, researchers from the Xinxiang Medical University in China conducted a review of 89 randomized controlled trials involving nearly 30,000 participants. The studies examined EGFR tyrosine kinase inhibitor use on patients with non-small cell lung cancer.

Led by Dr. Zidong Ma, the team determined that first gen drugs like Tarceva and third gen drugs like Tagrisso were both linked to an increased risk of cardiovascular side effects. Compared to placebo, Tarceva increased the risk of cardiac events by 51%, while Tagrisso increased the risk of cardiac side effects by more than 100%.

The incidence of cardiac side effects among first gen drugs like Tarceva and Iressa were 3% compared to nearly 10% in third gen drugs like Tagrisso and Lacluze. Cardiac events included arrhythmias, hypertension, stroke, blood clots and heart failure.

The data also showed that when some cancer drugs were combined, the risk increased even more. Combining antiangiogenesis drugs like Avastin with third generation Tagrisso increased the risk of hypertension, arrhythmias and heart failure, according to the findings.

“This network meta-analysis highlighted varying risks of cardiovascular adverse drug reactions across first and third generation EGFR tyrosine kinase inhibitors, with third generation inhibitors associated with a noticeably higher risk of cardiotoxicity.”

— Dr. Zidong Ma, Cardiovascular adverse events associated with epidermal growth factor receptor tyrosine kinase inhibitors in EGFR-mutated non-small cell lung cancer: systematic review and network meta-analysis

Researchers concluded third generation EGFR inhibitors were linked to higher cardiac risks overall, compared with first generation inhibitors. However, they warned that more research is needed to fully explore the differences, and that doctors should take the risks into consideration when prescribing medications for patients.

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