Medication patterns of abiraterone acetate plus prednisone or enzalutamide and PSA progression in veterans with metastatic castration-resistant prostate cancer

Freedland, Stephen J.; Li, Sophia; Pilon, Dominic; Bhak, Rachel H.; Narkhede, Sahil; Lefèbvre, Patrick; Young‐Xu, Yinong

doi:10.1080/03007995.2021.1888704

Cited by 8 publications

(6 citation statements)

References 22 publications

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“…Moreover, dose reductions were seen in 64.4% of all study patients and were associated with 8.8% increased risk of biochemical progression. Dose reductions are relevant given that the combination of ENZ with a CYP2C8 inhibitor can increase ENZ levels by 2.2-fold, thereby potentially requiring a lower dose [ 46 ].…”

Section: Resultsmentioning

confidence: 99%

Outcomes Following Abiraterone versus Enzalutamide for Prostate Cancer: A Scoping Review

Shah

Shaver

Beiriger

et al. 2022

Cancers

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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.

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Section: Resultsmentioning

confidence: 99%

Outcomes Following Abiraterone versus Enzalutamide for Prostate Cancer: A Scoping Review

Shah

Shaver

Beiriger

et al. 2022

Cancers

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“…Consistently, Freedland et al reported that dose reduction was associated with a significantly higher risk of PSA progression when administering abiraterone or enzalutamide in a group of 6,069 veterans with metastatic CRPC. 17 Meanwhile, Vinh-Hung et al reported that the PSA decline and PFS were comparable between low-dose (≤80 mg/day) and standard-dose enzalutamide among patients ≥75 years old. 18 However, this study retrospectively included only 59 elderly patients, of whom 16 received low-dose and 43 standard-dose therapies, suggesting insufficient statistical power.…”

Section: Discussionmentioning

confidence: 99%

Prognostic impact of dose reduction in androgen receptor pathway inhibitors for castration-resistant prostate cancer

Yamada

Shiota

Blas

et al. 2022

Prostate International

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“…A retrospective, longitudinal cohort study of 6069 US veterans with metastatic CRPC explored the impact of relative dose intensity (RDI) of enzalutamide on PSA progression (defined as PSA ≥2 ng/mL and ≥25% above the nadir). 26 In total, 924 (67.2%) men taking enzalutamide had at least one RDI <80% over at least 2 months, and this was associated with a higher risk of PSA progression (HR 1.26, 95% CI 1.09 to 1.46). No assessment of the impact of lower enzalutamide doses on PFS or OS was performed due to limited data.…”

Section: Retrospective Analysesmentioning

confidence: 97%

Comparison of standard-dose and reduced-dose treatment of metastatic prostate cancer with enzalutamide, apalutamide or darolutamide: a rapid review

Bromley,

Varughese,

Gilbert

et al. 2024

bmjonc

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ObjectiveTo review the efficacy and safety of low-dose versus standard-dose enzalutamide, apalutamide or darolutamide treatment for metastatic prostate cancer.Methods and analysisKeyword searches in MEDLINE and EMBASE up to 1 June 2023, with forward and backward citation searches of potentially relevant studies. Studies were included if primary outcome data were reported for patients with metastatic prostate cancer who had received reduced doses of enzalutamide, apalutamide or darolutamide. Searches were limited to original full-text and English-language studies. Key outcomes included overall survival (OS), progression-free survival (PFS), prostate-specific antigen response and treatment-related adverse events. The review was performed in accordance with Cochrane Rapid Reviews Methods Group guidelines.ResultsTen studies were identified that met the eligibility criteria: five phase I studies, two post-hoc analyses of phase III trials and three retrospective analyses. No consistent association between OS, PFS and drug dose was identified. Fewer severe treatment-related adverse events were observed at lower drug doses.ConclusionThis review provides evidence that enzalutamide, apalutamide or darolutamide could be given at a lower than the standard recommended dose without loss of antitumour activity. A prospective near-equivalence randomised trial should be undertaken to compare registered and lower doses of these agents.PROSPERO registration numberCRD42023440371.

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Medication patterns of abiraterone acetate plus prednisone or enzalutamide and PSA progression in veterans with metastatic castration-resistant prostate cancer

Cited by 8 publications

References 22 publications

Outcomes Following Abiraterone versus Enzalutamide for Prostate Cancer: A Scoping Review

Outcomes Following Abiraterone versus Enzalutamide for Prostate Cancer: A Scoping Review

Prognostic impact of dose reduction in androgen receptor pathway inhibitors for castration-resistant prostate cancer

Comparison of standard-dose and reduced-dose treatment of metastatic prostate cancer with enzalutamide, apalutamide or darolutamide: a rapid review

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