Dataset Information

Hormonal Therapeutics Enzalutamide and Abiraterone Acetate in the Treatment of Metastatic Castration-Resistant Prostate Cancer (mCRPC) Post-docetaxel-an Indirect Comparison.

ABSTRACT:

Introduction

This study aims to make an indirect comparison between enzalutamide and abiraterone acetate for mCRPC post-docetaxel.

Methods

A search for published phase 3 trials was performed with PubMed. Indirect comparisons of enzalutamide (AFFIRM) to abiraterone acetate (COU-AA-301) on outcomes overall survival (OS), time to prostate-specific-antigen (PSA) progression, radiographic progression-free survival (PFS), and PSA response were constructed in the context of log-linear regression models.

Results

There was no statistically significant difference in OS (hazard ratio (HR) 0.85, 95% CI 0.68-1.07). However, there was some evidence that enzalutamide may outperform abiraterone acetate with respect to secondary outcomes: time to PSA progression (HR 0.40, 95% CI 0.30-0.53), radiographic PFS (HR 0.61, 95% CI 0.50-0.74), and PSA response rates (RRs) (OR 10.69, 95% CI 3.92-29.20).

Conclusion

While there was no statistically significant difference in OS, enzalutamide may be advantageous for secondary endpoints. Findings of this indirect comparison serve to be hypothesis-generating for future head-to-head trials.

SUBMITTER: Tan PS

PROVIDER: S-EPMC3964205 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Publications

Hormonal Therapeutics Enzalutamide and Abiraterone Acetate in the Treatment of Metastatic Castration-Resistant Prostate Cancer (mCRPC) Post-docetaxel-an Indirect Comparison.

Tan Pui S PS Haaland Benjamin B Montero Alberto J AJ Kyriakopoulos Christos E CE Lopes Gilberto G

Clinical Medicine Insights. Oncology 20140316

<h4>Introduction</h4>This study aims to make an indirect comparison between enzalutamide and abiraterone acetate for mCRPC post-docetaxel.<h4>Methods</h4>A search for published phase 3 trials was performed with PubMed. Indirect comparisons of enzalutamide (AFFIRM) to abiraterone acetate (COU-AA-301) on outcomes overall survival (OS), time to prostate-specific-antigen (PSA) progression, radiographic progression-free survival (PFS), and PSA response were constructed in the context of log-linear re ...[more]

PMID: 24678245

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Project description:BackgroundIt is hypothesised that cotargeting the androgen receptor (AR) and paracrine androgen biosynthesis with enzalutamide and abiraterone acetate in metastatic castration-resistant prostate cancer (mCRPC) will dissipate adaptive feedback loops observed with either agent alone.ObjectiveTo assess the safety, efficacy, androgen signalling/metabolome, and drug-drug interactions (DDIs) of enzalutamide with abiraterone acetate in progressive bone mCRPC (bmCRPC).Design, setting, and participantsThis open-label, single-centre interventional study was conducted in bmCRPC patients.InterventionEnzalutamide 160mg and abiraterone acetate 1000mg once daily; prednisone 5mg twice daily.Outcome measurements and statistical analysisAdverse events (AEs), prostate-specific antigen (PSA) response, progression-free survival (PFS), tumour biomarker/metabolite expression, and Cmin plasma concentrations were evaluated.Results and limitationsSixty patients were enrolled. Common AEs independent of grade/causality included fatigue (72%), hyperglycaemia (67%), alkaline phosphatase (ALP) elevation (53%), and hot flush (43%). Grade 3 AEs included hypertension (17%), alanine aminotransferase elevation (12%), ALP elevation (5%), and arthralgia (5%). No treatment-related grade 4 AEs or deaths were reported. Median treatment-discontinuation time was 312d (95% confidence interval [CI] 196.0-483.0). Maximal PSA decline ≥50% and ≥90% occurred in 46 (77%) and 29 (48%) patients, respectively. Median PFS was 251d (95% CI 147-337). At week 9, median tumour microenvironment androgens, precursors, and nuclear AR expression decreased (p<0.001). The baseline tumour AR C/N terminal ratio of ≥80% was associated with treatment benefit. At enzalutamide steady state, abiraterone acetate Cmin was ∼23% lower (range 14.05-200.5ng/ml) than when given alone.ConclusionsEnzalutamide combined with abiraterone acetate has a manageable safety profile, without a meaningful DDI. Both agents are pharmacodynamically active with no feedback. Efficacy findings do not support significant benefit of combined treatment for unselected bmCRPC.Patient summaryThis is the first study combining enzalutamide plus abiraterone in bone metastatic castration-resistant prostate cancer. Results show that this combination is safe.

Project description:ObjectiveEvaluation of the comparative effectiveness of enzalutamide and abiraterone in patients with metastatic castration-resistant prostate cancer (mCRPC) is limited to meta-analyses of randomized trials that exclude patients with significant comorbidities. We evaluated overall survival (OS) in patients with chemotherapy-naive mCRPC treated with enzalutamide or abiraterone acetate (abiraterone) in a real-world single payer setting.MethodsA retrospective analysis (4/1/2014-3/31/2018) of the Veterans Health Administration (VHA) database was conducted. Patients with mCRPC had ≥1 pharmacy claim for enzalutamide or abiraterone (first claim date = index date) following disease progression on surgical/medical castration, without chemotherapy <12 months prior to index date. Patients had continuous VHA enrollment for ≥12 months pre-index date and were followed until death, disenrollment, or end of study. Kaplan-Meier analysis and multivariable Cox proportional hazards regression models examined the OS treatment effect.ResultsPatients with chemotherapy-naive mCRPC (N = 3174; enzalutamide, n = 1229; abiraterone, n = 1945) had mean ages of 74 and 73 years, respectively. Median follow-up was 18.27 and 19.07 months with enzalutamide and abiraterone, respectively. Enzalutamide-treated patients had longer median treatment duration than abiraterone-treated patients (9.93 vs 8.47 months, respectively, p = 0.0008). After baseline comorbidity adjustment, enzalutamide-treated patients had a 16% reduced risk of death (hazard ratio [HR] = 0.84; 95% CI, 0.76-0.94; p = 0.0012). For patients who remained on first line-therapy only, enzalutamide-treated patients had improved OS versus abiraterone-treated patients (HR = 0.71; 95% CI, 0.62-0.82). Enzalutamide-treated patients who crossed over to abiraterone had a comparable risk of death versus abiraterone-treated patients who crossed over to enzalutamide (HR = 1.10; 95% CI, 0.89-1.35). These results were confirmed by sensitivity analysis, which considered prognostic variables.ConclusionsRetrospective analysis of the VHA database indicated that chemotherapy-naive patients with mCRPC initiating therapy with enzalutamide had improved survival versus abiraterone.

Project description: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.

Dataset Information

Hormonal Therapeutics Enzalutamide and Abiraterone Acetate in the Treatment of Metastatic Castration-Resistant Prostate Cancer (mCRPC) Post-docetaxel-an Indirect Comparison.

Introduction

Methods

Results

Conclusion

Publications

Hormonal Therapeutics Enzalutamide and Abiraterone Acetate in the Treatment of Metastatic Castration-Resistant Prostate Cancer (mCRPC) Post-docetaxel-an Indirect Comparison.

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