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Oral prostate cancer therapies increase mortality risk for men with cardiovascular conditions
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Abiraterone acetate and enzalutamide appeared to increase the risk for death among older men with advanced prostate cancer and pre-existing cardiovascular conditions, according to results of a population-based retrospective study published in European Urology.
“Most cancer therapies have side effects. It is important to evaluate whether the benefits of the drug outweigh its risks,” Grace Lu-Yao, PhD, MPH, professor and vice chair of medical oncology at Thomas Jefferson University and associate director of population science at Sidney Kimmel Cancer Center, told HemOnc Today. “For patients with a high baseline risk for [cardiovascular disease], the risk of an adverse [cardiovascular] event might outweigh the benefits of slowing down cancer progression. It depends on the life expectancy of the patients and the aggressiveness of prostate cancer.”
Clinical trials involving abiraterone acetate (Zytiga, Janssen Oncology) or enzalutamide (Xtandi; Astellas, Pfizer) typically exclude men aged 65 years or older with advanced prostate cancer and significant comorbidities, such as cardiovascular disease (CVD) or uncontrolled hypertension. As a result, limited data exist on the effects of the drugs on these men, researchers noted.
In this retrospective, population-based study, Lu-Yao and colleagues used the SEER database to analyze 3,876 older men with advanced prostate cancer treated with abiraterone acetate (n = 2,845) or enzalutamide (n = 1,031). Two-thirds of the men (67%) had at least one pre-existing CVD condition.
All-cause mortality by 6 months served as the primary endpoint. Researchers analyzed this endpoint using modified Poisson regression modeling of relative risk adjusted for confounders and comorbidities. Inpatient hospitalization 6 months before and 6 months after initiation of abiraterone acetate or enzalutamide served as secondary endpoints.
Results showed that one or two pre-existing CVD conditions appeared associated with a 16% higher risk for 6-month mortality (RR = 1.16; 95% CI, 1-1.36) compared with no pre-existing CVD conditions. Men with three or more pre-existing cardiovascular disease conditions had a 56% increased risk for 6-month mortality (RR = 1.56; 95% CI, 1.29-1.88).
Researchers stratified men by chemotherapy status for multivariable analysis.
Based on crude incidence rate ratios, abiraterone acetate appeared associated with higher hospitalization rates regardless of pre-existing CVD conditions among men who did not receive chemotherapy.
Researchers observed no significant differences in hospitalization rates between the drugs among patients who had received chemotherapy. However, post-chemotherapy patients with one or two CVD conditions had a 43% higher hospitalization rate compared with patients who did not have a CVD condition (incidence rate ratio [IRR] = 1.43; 95% CI, 1.15-1.78).
Among men who did not receive chemotherapy and had three or more CVD conditions, those treated with enzalutamide vs. abiraterone acetate had a 41% lower hospitalization rate (IRR = 0.59; 95% CI, 0.44-0.79).
Treatment efficacy could not be determined because of the study’s retrospective nature, which served as its primary limitation.
“I would not recommend against prescribing these drugs to patients with cardiovascular disease conditions at this time,” Lu-Yao said. “For patients with pre-existing CVD conditions, I recommend that these patients be managed by the care team with a cardiologist, who can monitor the CVD risk and take necessary steps when needed.” – by John DeRosier
For more information:
Grace Lu-Yao, PhD, MPH, can be reached at Thomas Jefferson University, BLSB 812, 233 S. 10th St., Philadelphia, PA, 19107; email: grace.luyao@jefferson.edu.
Disclosures: The authors report no relevant financial disclosures.
Perspective
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Austin N. Kirschner, MD, PhD
The publication by Lu-Yao and colleagues adds to the growing literature about the cardiovascular-related risks of androgen deprivation therapies that are in widespread clinical use for treatment of advanced prostate cancer. This patient population typically is elderly and has a significant rate of preexisting cardiovascular disease.
Although abiraterone and enzalutamide are standard treatments for advanced prostate cancer and provide survival advantages from a cancer-specific perspective, it is important to consider their impact on noncancer health, especially from a cardiovascular perspective. As the study indicates, even a common ailment such as hypertension can increase the risks for hospitalization following initiation of abiraterone or enzalutamide. Although the exact mechanism is not well-understood, associations between these drugs and cardiovascular outcomes are implied by these data, including alterations in metabolic pathways, drug-drug interactions and body changes associated with cardiovascular risks.
My routine clinical practice includes referral to a cardiologist for patients who are initiating ADT. Even if a patient has an established cardiologist, it is prudent to notify of the anticipated drug therapy so that additional consideration of the risks can be given. This way, patients can be evaluated for any undiagnosed or uncontrolled cardiovascular issues, and interventions can be administered before initiating an oral antiandrogen therapy. Further, there is a growing field of cardiologists who specialize in oncology, and they are extremely valuable collaborative partners in patient care.
Optimizing cardiovascular health parameters and addressing ongoing and impending cardiovascular problems would allow greater latitude with the use of ADT. Given the increased hospitalizations and mortality risk, it is prudent to monitor patients more carefully during the first 6 months after initiating ADT, with a focus on cardiovascular health.
As patients live longer as a result of cancer management, competing cardiovascular risks become important to consider for optimal patient outcomes. Large database analyses and ongoing surveillance of adverse drug-related outcomes are critical to improving patient care by selecting the appropriate treatment approach that balances the benefits and risks in a most favorable ratio.
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