Common prostate cancer drugs may elevate risk for metabolic, cardiovascular adverse events
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Key takeaways:
- Men treated with abiraterone had increased risks for a major composite adverse event and a minor composite adverse event.
- Men treated with enzalutamide had significantly increased risk for a major composite adverse event but not a minor composite event.
- Abiraterone may be a less preferred option for men at higher risk for metabolic and cardiovascular adverse events.
Both abiraterone and enzalutamide appeared to increase risk for metabolic and cardiovascular adverse events among older men with advanced prostate cancer who previously underwent androgen deprivation therapy, according to study results.
The findings, published in Journal of the National Cancer Institute, showed men treated with abiraterone (Zytiga, Janssen) experienced a 1.77-fold increased risk for ER or hospital admission for diabetes, hypertension or heart disease compared with those who underwent ADT only, and men treated with the androgen receptor antagonist enzalutamide (Xtandi; Astellas, Pfizer) had a 1.22-fold increased risk for these adverse events, researchers noted.
Rationale and methods
Abiraterone and enzalutamide, widely used drugs for treatment of advanced prostate cancer, have exhibited favorable safety profiles in clinical trials, but their safety in real-world settings has not been studied extensively, according to researchers.
“Patients enrolled in clinical trials tend to be highly selected and often do not reflect the patient population in day-to-day practice,” Lillian Y. Lai, MD, MS, an NIH T32 urologic oncology research fellow at Michigan Medicine, said in a press release. “Trial participants also undergo stringent safety evaluations that some of our patients do not have access to. By studying adverse events in real-life settings, we can better understand the risks of these life-prolonging cancer treatments and help clinicians and patients make informed decisions regarding treatment.”
The study included 56,230 men from a sample of national Medicare claims with advanced prostate cancer between 2010 and 2017.
Compared with men not treated with either therapy, those treated with abiraterone or enzalutamide (n = 3,942) were younger (median age, 78.8 years vs. 76.8 years), healthier (44% vs. 49.6% with comorbidity score of zero) and more likely to be white (86% vs. 84.1%).
Researchers used Cox regression analysis to separately assess risks for abiraterone vs. enzalutamide, and all statistical tests were two-sided.
Occurrence of a major metabolic or cardiovascular adverse event, defined as an ER visit or hospitalization associated with first diagnosis of diabetes, hypertension or cardiovascular disease, served as the primary composite outcome. Occurrence of a minor metabolic or cardiovascular adverse event, defined as an outpatient visit associated with a primary diagnosis of the conditions, served as the secondary composite outcome.
Key findings
Results showed men treated with abiraterone had increased risks for a major composite adverse event (HR = 1.77; 95% CI, 1.53-2.05) and a minor composite adverse event (HR = 1.24; 95% CI, 1.05-1.47).
However, researchers observed significantly increased risk for a major composite adverse event (HR = 1.22; 95% CI, 1.01-1.48) but not a minor composite event (HR = 1.04; 95% CI, 0.83-1.3) among men treated with enzalutamide.
Implications
“With continued expansion of the indications for abiraterone and enzalutamide to earlier stages of the disease continuum, increasing numbers of men will be receiving these therapies for longer periods of time,” Lai and colleagues wrote. “This will potentially amplify the scope of men affected and increase the magnitude of the risks [for] adverse events, making careful attention to management of these issues crucial.”
Because the risks for metabolic and cardiovascular adverse events are more pronounced with abiraterone vs. enzalutamide, abiraterone may be a less preferred option for men at higher risk for metabolic and cardiovascular adverse events, researchers added.
“Another consideration is that metabolic and cardiovascular conditions are generally managed by primary care providers,” they wrote. “Team-based care involving patients’ primary care providers may help mitigate these adverse events so that men with advanced prostate cancer can remain on life-prolonging cancer therapies longer and with less disruption to their quality of life.”
References:
- Common prostate cancer medications may be less safe than previously thought (press release). Available at: www.sciencedaily.com/releases/2022/05/220525151750.htm. Published May 25, 2022. Accessed Aug. 4, 2022.
- Lai LY, et al. J Natl Cancer Inst. 2022;doi:10.1093/jnci/djac081.
Perspective
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Christopher Wee, MD
We have made significant advancements in the treatment of advanced prostate cancer over the past decade. Historically, men with metastatic hormone-sensitive prostate cancer had been treated with ADT alone with or without chemotherapy (docetaxel). However, current standard-of-care options incorporate the addition of novel hormonal agents given improved OS across multiple randomized trials. Novel hormonal agents — including apalutamide (Erleada, Janssen), enzalutamide (Xtandi; Astellas, Pfizer), darolutamide (Nubeqa, Bayer) and abiraterone acetate (Zytiga, Janssen) — are critical components of effective care for patients with advanced prostate cancer.
As prostate cancer-related outcomes continue to improve, the cumulative risk for noncancer-related morbidity and mortality likely will increase. Cardiac toxicities of ADT have been known; ADT itself is associated with increased risk for adverse cardiac events. The authors found that adding abiraterone acetate or enzalutamide to ADT was associated with even further cardiac toxicity. However, treatment decisions based on concerns of increased cardiac risk with novel hormonal agents should not supersede the multiple prospective, randomized controlled trial data demonstrating improved OS with novel hormonal agents. The findings of these authors should, however, re-emphasize the importance of managing noncancer comorbidities, including optimization of cardiac risk factors.
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