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Introduction: Abiraterone acetate and enzalutamide are commonly employed in prostate cancer therapy in an interchangeable manner. These drugs are highly efficacious in androgen antagonism to improve patient outcomes, but they also carry noteworthy risk of adverse effects. Common toxicities vary amongst the two drugs and may have differential interactions with patient co-morbidities, but these patterns are unclear as co-morbidities typically serve as exclusion criteria in clinical trials. Hence, there is no existing guidance on how clinicians may tailor treatment based on patient-specific factors. Analysis of differential patient outcomes between these two drugs can inform future systematic reviews, new clinical studies, and clinical decision making. Method and analysis: The framework for this methodology was informed by the Joanna Briggs Institute methodology for scoping reviews. Title and abstract screening will be performed by two independent researchers to create an initial study inventory. This will be followed by full-text screening for study inclusion. Population-based studies describing patient outcomes, common toxicities, and associations with patient co-morbidities following abiraterone or enzalutamide therapy will be included. After data is extracted, it will be summarized for presentation. Ethics and dissemination: The findings of this scoping review will be published in a peer-reviewed journal. The results will be used to inform future studies on patient-specific factors informing treatment choice between abiraterone and enzalutamide for castration-resistant prostate cancer. All data are from published openly accessible sources, and therefore, no ethical clearance is necessary. The protocol is also registered at https://doi.org/10.6084/m9.figshare.19149227. [ABSTRACT FROM AUTHOR]

Simple Summary: Abiraterone acetate and enzalutamide are novel therapies used in advanced prostate cancer. However, their outcomes and toxicities may differ based on patient–specific factors. Understanding these differences may allow clinicians to make personalized treatment decisions based on individual patients. Because clinical trials do not represent the real-world population, this study used a formal protocol to review and collate smaller, real-world samples, aiming to explain the differences in outcomes following administration of these two drugs. We found that enzalutamide typically has improved cancer response and overall survival. Enzalutamide more commonly causes neurological side effects and fatigue, while abiraterone acetate has cardiovascular complications. Abiraterone acetate leads to increased costs and healthcare needs, including hospitalizations and emergency room visits. Ultimately, this study demonstrates significant differences in patient experiences and outcomes following abiraterone acetate versus enzalutamide. Clinicians may use this information to inform their treatment choice on a patient-specific basis. Abiraterone acetate (AA) and enzalutamide (ENZ) are commonly used for metastatic prostate cancer. It is unclear how their outcomes and toxicities vary with patient-specific factors because clinical trials typically exclude patients with significant comorbidities. This study aims to fill this knowledge gap and facilitate informed treatment decision making. A registered protocol utilizing PRISMA scoping review methodology was utilized to identify real-world studies. Of 433 non-duplicated publications, 23 were selected by three independent reviewers. ENZ offered a faster and more frequent biochemical response (30–50% vs. 70–75%), slowed progression (HR 0.66; 95% CI 0.50–0.88), and improved overall survival versus AA. ENZ was associated with more fatigue and neurological adverse effects. Conversely, AA increased risk of cardiovascular- (HR 1.82; 95% CI 1.09–3.05) and heart failure-related (HR 2.88; 95% CI 1.09–7.63) hospitalizations. Ultimately, AA was associated with increased length of hospital stay, emergency department visits, and hospitalizations (HR 1.26; 95% CI 1.04–1.53). Accordingly, total costs were higher for AA, although pharmacy costs alone were higher for ENZ. Existing data suggest that AA and ENZ have important differences in outcomes including toxicities, response, disease progression, and survival. Additionally, adherence, healthcare utilization, and costs differ. Further investigation is warranted to inform treatment decisions which optimize patient outcomes. [ABSTRACT FROM AUTHOR]

Background. We hypothesized that Aurora A kinase (AK) contributes to castrate resistance in prostate cancer (PCa) and that inhibiting AK with alisertib can resensitize PCa cells to androgen receptor (AR) inhibitor abiraterone. Methods. This was a phase I/II trial to determine the safety and efficacy of alisertib when given in combination with abiraterone plus prednisone (AP). Metastatic castration-resistant prostate cancer (mCRPC) patients were treated with dose escalation (alisertib at 30,40, and 50 mg orally b.i.d., days 1-7 every 21 days) per standard 3 + 3 design. Results. Nine of 43 planned subjects were enrolled. The maximum tolerated dose (MTD) was not reached, and the dose-limiting toxicities (DLTs) included neutropenic fever (1 of 9), neutropenia (1 of 9), fatigue with memory impairment (1 of 9), and diarrhea/mucositis (1 of 9). No prostate-specific antigen (PSA) decrease or circulating tumor cell (CTC) changes were observed during the study. Pharmaco-dynamically, adding alisertib did not affect total testosterone or dehydroepiandrosterone (DHEA) levels. There was some change in neuroendocrine markers after therapy. Mean duration on study was 2.5 months. The trial was terminated early. Conclusion. A tolerable dose of alisertib in combination with AP in mCRPC was not established in this study. There was no clear signal indicating that alisertib might be beneficial for patients with mCRPC progressing on abiraterone. [ABSTRACT FROM AUTHOR]

Elderly patients (≥65 yr) with advanced prostate cancer and cardiovascular disease (CVD) conditions are often excluded from clinical trials of abiraterone acetate (AA) or enzalutamide (ENZ). Consequently, little is known about the effects of these medications on these vulnerable patients. To assess the short-term outcomes of AA and ENZ in patients with pre-existing CVDs. A population-based retrospective study. The Surveillance, Epidemiology, and End Results-Medicare–linked database was used to identify prostate cancer patients using AA or ENZ. The primary endpoint was 6-mo all-cause mortality, analyzed using modified Poisson regression modeling of relative risk (RR) adjusted for confounders and comorbidities. Among eligible patients (2845 with AA and 1031 with ENZ), 67% had at least one pre-existing CVD. Compared with those without pre-existing CVDs, having one to two pre-existing CVDs was associated with 16% higher 6-mo mortality (RR = 1.16, 95% confidence interval [CI]: 1.00–1.36), and the risk increased further among those having three or more CVDs (RR = 1.56, 95% CI: 1.29–1.88). Most of the differences in survival of patients with pre-existing CVD condition occurred within the first 6 mo of treatment. After treatment with AA or ENZ, elderly prostate cancer patients with pre-existing CVDs experienced higher short-term mortality than otherwise similar patients without CVDs. Mortality associated with CVDs did not depend on having received AA versus ENZ. Patients with pre-existing cardiovascular diseases (CVDs) experienced higher short-term mortality after abiraterone acetate or enzalutamide than those without pre-existing CVDs. It is recommended that a multidisciplinary team, including a cardiologist, evaluate patients having pre-existing CVDs in the process of making treatment decisions and monitoring potential side effects. Pre-existing cardiovascular conditions are associated with higher short-term mortality after abiraterone acetate or enzalutamide. The survival benefit observed in the pivotal clinical trials might not hold for patients with significant pre-existing cardiovascular conditions. [ABSTRACT FROM AUTHOR]