The Cardiovascular Toxicity of Abiraterone and Enzalutamide in Prostate Cancer

Iacovelli, Roberto; Ciccarese, Chiara; Bria, Emilio; Romano, Mario R.; Fantinel, Emanuela; Bimbatti, Davide; Muraglia, A.; Porcaro, Antonio Benito; Siracusano, Salvatore; Brunelli, Matteo; Mazzarotto, Renzo; Artibani, Walter; Tortora, Giampaolo

doi:10.1016/j.clgc.2017.12.007

Cited by 139 publications

(104 citation statements)

References 21 publications

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“…This impact was lower for all grade events. The relative risk of CV events with enzalutamide was lower than that for arbiraterone acetate (29,56). Two systematic reviews examined incidence of cognitive impairment from ADT (16,26).…”

Section: Cardiac Disorders: Cardiovascular (Cv) Complications and Mormentioning

confidence: 99%

“…ADT, particularly second generation hormonal agents such as abiraterone acetate and enzalutamide, is associated with significant increases in risk of hypertension. Four systematic reviews generated data on the incidence of hypertension for men receiving ADT for PC (22,29,56,57). One showed a higher incidence of long-term hypertension with radiotherapy and GnRH agonists than with the use of antiandrogens (12% vs 4%) (57).…”

Section: A Hypertensionmentioning

confidence: 99%

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Incidence of the adverse effects of androgen deprivation therapy for prostate cancer: a systematic literature review

Edmunds

Tuffaha

Galvão

et al. 2020

Support Care Cancer

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PurposeAndrogen deprivation therapy (ADT) has broad application in the treatment of prostate cancer (PC) and is associated with numerous, debilitating adverse effects. Increasing use of ADT for PC, longer timeframe for treatment (increased uptake of PSA testing and earlier diagnosis), as well as improved survival and an ageing population, means patients can live for a considerable period of time on or after ADT, experiencing these adverse effects. A number of systematic reviews of adverse effects of ADT for PC exist, however, no single systematic review has previously examined the evidence for all adverse effects, including newer forms of ADT. MethodsA systematic review of existing systematic reviews of ADT for PC was conducted (2010 -February 2019), as per Cochrane guidelines, to identify the highest level of risk/incidence evidence available, supplemented by evidence drawn from individual studies where no systematic review existed. ResultsIncidence data was generated for 19 adverse effect sub groups, classified according to the common terminology criteria for adverse events (CTCAE). ConclusionIncidence of adverse effects provides valuable information for future burden of disease studies. This information can better guide clinical management to reduce symptoms for patients and assist patients to make more informed decisions about their treatment, potentially improving disease outcomes. It also highlights the importance of supportive care for PC patients receiving ADT and their carers. For analysts conducting economic evaluations, the inclusion of adverse effects in PC decision analytic models can provide more comprehensive and accurate information for decision makers.

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Section: Cardiac Disorders: Cardiovascular (Cv) Complications and Mormentioning

confidence: 99%

Section: A Hypertensionmentioning

confidence: 99%

Incidence of the adverse effects of androgen deprivation therapy for prostate cancer: a systematic literature review

Edmunds

Tuffaha

Galvão

et al. 2020

Support Care Cancer

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“…Although treatment with enzalutamide demonstrated an overall greater risk of incident hypertension, only abiraterone was associated with a significantly increased risk of high-grade hypertension, observed in 6.9% of patients, irrespective of concomitant prednisone dose. 12 ADT AND CARDIOVASCULAR DISEASE The above-mentioned changes create an atherogenic risk profile through which ADT has been proposed to cause cardiovascular disease. A number of studies have demonstrated that ADT is associated with fatal and nonfatal cardiovascular disease events that encompass ischemic heart disease, myocardial infarction, sudden cardiac death or ventricular arrhythmias, cerebrovascular accidents, peripheral artery disease, and venous thromboembolism.…”

Section: Adt Insulin Resistance and Diabetes Mellitusmentioning

confidence: 99%

“…Although the incidence of high-grade cardiovascular events with treatment with abiraterone was low at 4.5%, this translates to a more than two-fold increased risk compared with placebo. 12 Some studies have suggested a greater risk of fatal cardiovascular disease 3 and a shorter time to fatal myocardial infarctions 32 with ADT in the subset of patients older than age 65 years. A study by Ziehr et al 33 demonstrated an association between ADT and cardiac-specific mortality only in patients with a history of coronary disease-induced heart failure or myocardial infarction.…”

Section: Current Literature and Controversies In Adt And Cardiovasculmentioning

confidence: 99%

“…Both abiraterone and enzalutamide have been approved for use in metastatic castration-resistant prostate cancer, and recently, in metastatic hormone-sensitive-or hormone-naïve-disease. 12 Cardiovascular disease represents the most common comorbidity and cause of death among patients with prostate cancer. 11,13,14 The risk of cardiovascular disease was found to be higher in patients with prostate cancer compared with the general population.…”

Section: Introductionmentioning

confidence: 99%

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Cardiovascular and Metabolic Effects of Androgen-Deprivation Therapy for Prostate Cancer

Gupta

Chuy

Yang

et al. 2018

JOP

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Androgen-deprivation therapy (ADT) entails lowering serum testosterone levels to castrate levels and forms a cornerstone of the management of hormone-sensitive advanced prostate cancer; however, the benefit of ADT is partially offset by its detrimental metabolic and cardiovascular adverse effects. ADT decreases insulin sensitivity while promoting dyslipidemia and sarcopenic obesity, which leads to an increased risk of cardiovascular morbidity and potentially mortality. The risk seems to be highest in elderly patients who have had recent cardiovascular events before starting ADT. It is prudent to engage in an individualized risk-benefit discussion and develop a cohesive multidisciplinary management plan to medically optimize and closely observe these patients before and during treatment with ADT.Careful history taking and physical examination to diagnose, treat, and optimize active CV disease with guideline-directed therapy before starting androgen-deprivation therapyConsider metformin for diabetes, ACEIs for HTN, aspirin for vascular health, and statins for hyperlipidemia in eligible patientsSmoking cessation, lifestyle modification, exercise, and stress reduction must be emphasized in all patients Awareness to seek immediate medical attention for new or worsening CV symptoms Abbreviations: ACEI, angiotension-converting enzyme inhibitor; CV, cardiovascular; HTN, hypertension.

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Abiraterone or Enzalutamide for Patients With Metastatic Castration-Resistant Prostate Cancer

La,

Wang,

Corrigan

et al. 2024

JAMA Netw Open

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ImportanceAbiraterone acetate and enzalutamide are recommended as preferred treatments for metastatic castration-resistant prostate cancer (mCRPC), but differences in their relative efficacy are unclear due to a lack of head-to-head clinical trials. Clear guidance is needed for making informed mCRPC therapeutic choices.ObjectiveTo compare clinical outcomes in patients with mCRPC treated with abiraterone acetate or enzalutamide.Design, Setting, and ParticipantsThis retrospective, multicenter cohort study included patients with mCRPC in the US Department of Veterans Affairs health care system who initiated treatment with abiraterone acetate or enzalutamide between January 1, 2014, and October 30, 2022.ExposuresAbiraterone acetate or enzalutamide.Main Outcomes and MeasuresThe study used inverse probability of treatment weighting to balance baseline characteristics between patients initiating abiraterone acetate or enzalutamide and evaluated restricted mean survival time (RMST) differences in overall survival (OS), prostate cancer–specific survival (PCS), time to next treatment switching or death (TTS), and time to prostate-specific antigen (PSA) response (TTR) at different time points after treatment initiation.ResultsThe study included 5779 patients (median age, 74.42 years [IQR, 68.94-82.14 years]). Median follow-up was between 38 and 60 months. Patients initiating enzalutamide on average had longer OS than those initiating abiraterone acetate, with RMSTs of 24.29 months (95% CI, 23.58-24.99 months) and 23.38 months (95% CI, 22.85-23.92 months), respectively, and a difference in RMST of 0.90 months (95% CI, 0.02-1.79 months) at 4 years. Similarly, TTS and TTR were improved in patients initiating enzalutamide, with an RMST at 4 years of 1.95 months (95% CI, 0.92-2.99 months) longer for TTS and 3.57 months (95% CI, 1.76-5.38 months) shorter for TTR. For PCS, the RMST at 2 years was 0.48 months (95% CI, 0.01-0.95 months) longer. An examination of subgroups identified that enzalutamide initiation was associated with longer RMST in OS among patients without prior docetaxel treatment (1.14 months; 95% CI, 0.19-2.10 months) and in those with PSA doubling time of 3 months or longer (2.23 months; 95% CI, 0.81-3.66 months) but not among patients with prior docetaxel (−0.25 months; 95% CI, −2.59 to 2.09 months) or with PSA doubling time of less than 3 months (0.05 months; 95% CI, −1.05 to 1.15 months).Conclusions and RelevanceIn this cohort study of patients with mCRPC, initiation of enzalutamide was associated with small but statistically significant improvements in OS, PCS, TTS, and TTR compared with initiation of abiraterone acetate. The improvements were more prominent in short-term outcomes, including TTS and TTR, and in patient subgroups without prior docetaxel or with PSA doubling time longer than 3 months.

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The Cardiovascular Toxicity of Abiraterone and Enzalutamide in Prostate Cancer

Cited by 139 publications

References 21 publications

Incidence of the adverse effects of androgen deprivation therapy for prostate cancer: a systematic literature review

Incidence of the adverse effects of androgen deprivation therapy for prostate cancer: a systematic literature review

Cardiovascular and Metabolic Effects of Androgen-Deprivation Therapy for Prostate Cancer

Abiraterone or Enzalutamide for Patients With Metastatic Castration-Resistant Prostate Cancer

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