Adverse Effects on the Cardiovascular System in Men with Metastatic Castration-Resistant Prostate Cancer (mCRPC) Treated with Abiraterone or Enzalutamide - Editorial

Treatments for prostate cancer have rapidly evolved over the past nearly 10 years. Prior to this, the only approved life-prolonging agent for advanced prostate cancer was docetaxel. However, that all changed with the approval of abiraterone and enzalutamide. Both drugs showed profound benefits for men with metastatic castration-resistant prostate cancer (mCRPC). For these men, survival was measured in months and thus, the long-term toxicity of any therapies was not relevant. Acute toxicities were generally mild and manageable. As such, these agents made a huge impact and became widely used.

Newer data suggest that both abiraterone and enzalutamide also improve survival when given to men with metastatic castration-sensitive prostate cancer (mCSPC). For these men, survival is not measured in months, but rather years. As such, long-term toxicities become more relevant and are of keen interest.

Given that hormonal therapy is known to increase heart disease, it begs the question of whether abiraterone and enzalutamide, what I often refer to patients as “better hormonal therapy” vs. the traditional androgen deprivation therapy (ADT) alone also causes heart disease.

To answer this question, Lee and colleagues used data from various Phase II through Phase IV trials and performed a pairwise meta-analysis. They identified seven trials totaling 7,103 men. Upon doing this, the authors noted that abiraterone was associated with a 34% increased risk of any cardiac disorder and a 71% increased risk of several cardiac disorders, both of which were statistically significant. Similar data for enzalutamide showed a 28% increased risk of any cardiac disorder and a 24% increased risk of several cardiac disorders, neither of which was statistically significant. As such, the authors concluded that abiraterone has a greater risk of cardiac disorder.

The authors also examined hypertension. Herein, the authors found that abiraterone was associated with a 46% increased risk of any hypertension and a 29% increased risk of high-grade hypertension, which was significant only for any hypertension. Enzalutamide on the other hand was associated with a 166% increased risk of any hypertension and a 179% increased risk of high-grade hypertension, both of which were statistically significant.

The authors concluded that both abiraterone and enzalutamide had cardiac effects, but they were different. In short, despite both drugs having significant benefits including prolonged survival in multiple disease states, there is no free lunch. Both drugs have negative adverse effects on cardiovascular health. Importantly, as these agents are being used earlier and earlier in the disease course and thus for longer periods of time, it is likely the cardiovascular risks will be greater. 

In summary, we need to remember that we are physicians who pledged to do no harm. Both abiraterone and enzalutamide are life-prolonging drugs with a proven track record or helping patients. However, that does not mean they are without risks. Understanding these risks is crucial for appropriate patient selection and preventative measures including checking blood pressure, lipid panels, and working collaboratively with primary care doctors and cardiologists as needed. Together as a team, we can ensure that patients get the maximum benefit with minimal harm, but we first need to understand the potential harms, which this study nicely elucidates. It is often said, “It takes a village to raise a child”. Apparently, treating prostate cancer also takes a village.

Dr. Freedland reports being a consultant to Astellas, Pfizer, and Janssen – the makers of abiraterone and enzalutamide.

Written by: Stephen J. Freedland, MD, Director, Center for Integrated Research in Cancer and Lifestyle, Co-Director, Cancer Genetics, and Prevention Program, Associate Director, Faculty Development Samuel Oschin Comprehensive Cancer Institute, Professor of Surgery, Cedars-Sinai, Los Angeles, California

Read the Full-Text ArticleAbiraterone and Enzalutamide Had Different Adverse Effects on the Cardiovascular System: A Systematic Review with Pairwise and Network Meta-Analyses - Full Text Article

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