FDA Issued Postmarket CVD Safety Warning for 1 in 4 Cancer Drugs

The US Food and Drug Administration (FDA) has issued postmarket cardiac safety warnings for about 1 in 4 cancer therapies, according to a research letter published September 30 in JAMA Oncology.

These cardiotoxic risk communications typically were issued just over 4.5 years after a drug’s approval — 40% longer than it took to issue noncardiac warnings.

However, lead author Daniel Addison, MD, explained that the likelihood of having a major cardiac event related to a cancer drug appears to be quite small.

“I don’t think people should stop using cancer drugs that are saving lives,” said Addison, co-director of the Cardio-Oncology Program at the Ohio State University Comprehensive Cancer Center–James Cancer Hospital and Solove Research Institute, Columbus, Ohio. Rather, clinicians treating cancer patients should use a lower threshold for initiating a cardiovascular workup “if a patient is showing signs or symptoms of a potential heart issue.”

According to the researchers, cardiovascular events have become an increasingly common with the use of cancer therapies, but “the prevalence and factors associated with these warnings are unknown.”

That is why the team analyzed the frequency and timing of FDA postmarket cardiovascular communications for all anticancer therapies for which the FDA received new drug applications from 1998 to 2018. Communications included withdrawals, black box warnings, drug warnings, and precautions.

The authors found that of 125 FDA-approved cancer treatments, cardiovascular disease warning were issued for 32 (25.6%). Multiple warnings were issued for two dozen therapies (21.6%). Warnings were issued for more than 40% of the immune and targeted therapies — a total of 15 drugs. After arrhythmias (23.5%), uncontrolled hypertension (12%) and heart failure (11.4%) were the most common reasons for a cardiac safety communication.

“There’s been a lot of focus over the years, and rightly so, on heart failure, but I think in the last few years we’ve begun to appreciate other things that are going on with these patients,” said Addison, who noted a potential link between myocarditis and the use of immune checkpoint inhibitors.

Addison and colleagues also found that the median time for the FDA to issue postmarket alerts for cardiovascular events was 1670 days (55 months). In contrast, alerts related to noncardiac events occurred, on average, 15 months earlier — within 1120 days, or 40 months, of a treatment’s approval.

Addison noted that the average timing of cardiac safety communications masks wide variations by event type. Alerts regarding heart failure or hypertension, for example, emerged around 1200 days after a drug approval, but it took more than 2000 days for alerts about arrhythmias to be issued.

The authors said that the “delayed recognition is concerning, particularly given the rapid emergence of many targeted and immune-based cancer therapies, and the potentially devastating consequences of cardiotoxic events.”

Addison suggested that periodically analyzing medical registries could help experts detect cardiac signals linked to cancer treatments sooner.

In addition, more evidence about the potential cardiovascular risks associated with different anticancer drugs could help oncologists optimize care for their patients, according to Eiman Jahangir, MD, MPH, associate professor of medicine at Vanderbilt University Medical Center, Nashville, Tennessee, who was not involved in the study.

“In a lot of cases, these newer drugs are really changing how we treat cancer patients,” said Jahangir. “And typically, the benefit of curing a cancer outweighs the risk of a potential cardiac outcome, but as clinicians, we also need to know what [risks] to look for. If we know [about the risk for cardiac events], then we’re more likely to pick them up when a patient presents with symptoms.”

Jahangir and Addison have disclosed no relevant financial relationships. Several study coauthors reported receiving grants and personal fees from industry.

Marcus Banks reports on new health research, with a particular focus on cancer. His writing has appeared in Spectrum, Cancer Today, Nature Medicine, The Scientist, and Gastroenterology and Endoscopy News.

JAMA Oncol. Published online September 30, 2021. Full text

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