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ATLANTA -- An increased risk of early death was observed in men with pre-existing cardiovascular disease (CVD) starting abiraterone acetate (Zytiga) for advanced prostate cancer, a registry study found.

Among abiraterone-treated patients, increased mortality ranged from 21.4% for those with ischemic heart disease to 25.6% for those with acute myocardial infarction (MI), compared with 15.8% for those without a heart condition, reported Grace Lu-Yao, PhD, MPH, of the Sidney Kimmel Cancer Center at Thomas Jefferson University in Philadelphia.

"Our data show that patients with existing cardiovascular conditions experience significantly higher 6-month mortality than those without CVD," Lu-Yao said during a media briefing ahead of the American Association for Cancer Research (AACR) meeting, to be held here March 29-April 3.

Of the 2,845 patients in the study, 67.6% had a pre-existing heart condition (n=1,924). Patients with atrial fibrillation, congestive heart failure, and stroke had increased mortality risks of 24.4%, 23.4%, and 22.1%, respectively, within these first 6 months.

"Typically clinical trials do exclude people who have significant medical problems," said AACR President Elizabeth Jaffee, MD, of Johns Hopkins Medicine in Baltimore. "I think this has been rationalized as a safety measure by both investigators and sponsors."

In her presentation, Lu-Yao highlighted that roughly 40% of prostate cancer patients have uncontrolled hypertension. These patients, plus those with a history of major heart conditions, are usually excluded from clinical trials. In the STAMPEDE study, for instance, exclusion criteria included those with a history of severe angina or heart failure, and those with a recent MI.

Jaffe noted that testing new agents in the healthiest patients does not provide the real-world data physicians need.

The researchers used Surveillance, Epidemiology, and End Results (SEER)-Medicare linked data to look at prostate cancer patients treated with abiraterone from 2011 to 2014.

The study also found an increased risk of hospitalizations by examining hospital use in the 6 months before and after starting abiraterone treatment. Risk of hospitalization was increased for patients without a history of CVD for incidence rate ratios (IRR) 1.43 (95% CI 1.30-1.57), as well as for those with pre-existing CVD:

• Acute MI: IRR 1.44 (95% CI 1.12-1.86)
• Congestive heart failure: IRR 1.35 (95% CI 1.21-1.51)
• Stroke: IRR 1.30 (95% CI 1.07-1.57)
• Atrial fibrillation: IRR 1.27 (95% CI 1.09-1.48)
• Ischemic heart disease: IRR 1.22 (95% CI 1.01-1.48)

The study captured the period from when abiraterone was first approved by the FDA in 2011 for use in late-stage castration-resistant prostate cancer after prior treatment with docetaxel, and when it was then expanded in 2012 to also include use before chemotherapy. In the study, roughly 20% of the patients had received prior chemotherapy (n=586), with the rest being chemotherapy naive. Lu-Yao said that regardless of prior chemotherapy use, the patterns for both early mortality and hospitalization were "quite similar."

Jaffee noted that while the study is retrospective, it still provides important data, similar to that of a phase IV study.

"Once a drug's approved, all physicians can administer these drugs, and we don't really have a handle on who may have worse side effects from these drugs," she said. "We know that all therapies have side effects, and we need to be able to predict early, screen early, so we can at least monitor for these side effects and intervene at an early stage before patients have severe consequences from these drugs."

Study limitations included the possibility of misclassification of patients' CVD, the fact that treatment efficacy could not be assessed, and that there was no control group to look at expected survival for this patient population. A lack of clinical data also meant that the researchers could not compare the study population against the pivotal trials of abiraterone acetate.

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