DHODH inhibition represents a therapeutic strategy and improves abiraterone treatment in castration-resistant prostate cancer.

Castration-resistant prostate cancer (CRPC) is an aggressive disease with poor prognosis, and there is an urgent need for more effective therapeutic targets to address this challenge. Here, we showed that dihydroorotate dehydrogenase (DHODH), an enzyme crucial in the pyrimidine biosynthesis pathway, is a promising therapeutic target for CRPC. The transcript levels of DHODH were significantly elevated in prostate tumors and were negatively correlated with the prognosis of patients with prostate cancer. DHODH inhibition effectively suppressed CRPC progression by blocking cell cycle progression and inducing apoptosis. Notably, treatment with DHODH inhibitor BAY2402234 activated androgen biosynthesis signaling in CRPC cells. However, the combination treatment with BAY2402234 and abiraterone decreased intratumoral testosterone levels and induced apoptosis, which inhibited the growth of CWR22Rv1 xenograft tumors and patient-derived xenograft organoids. Taken together, these results establish DHODH as a key player in CRPC and as a potential therapeutic target for advanced prostate cancer.

Clinical outcomes in patients with metastatic castrate-resistant prostate cancer treated with abiraterone with or without ongoing androgen deprivation therapy: A retrospective case-control study.

INTRODUCTION: Abiraterone and concurrent androgen deprivation therapy (ADT) are used in the treatment of patients with metastatic castration-resistant prostate cancer. Recently, it has been suggested that the use of abiraterone alone (without ADT) may have comparable efficacy to abiraterone with ongoing ADT. Here, we sought to assess the impact of ADT cessation in patients beginning abiraterone for castration-resistant prostate cancer. METHODS: We identified 39 patients at our institution who received abiraterone alone (with discontinuation of ADT) between 2011 and 2022. We then procured a comparable group of 39 patients (matched by age, Gleason score, and prostate-specific antigen [PSA] level) who received abiraterone with ongoing ADT during the same period. We assessed and compared clinical outcomes in the two groups (abiraterone-alone vs. abiraterone-ADT) with respect to PSA response rates, PSA progression-free survival, and overall survival. Results were adjusted using Cox proportional-hazards multivariable models. RESULTS: The median PSA before treatment initiation was 12.7 (range: 0.2-199) ng/mL in the abiraterone-alone group and 15.5 (range: 0.6-212) ng/mL in the abiraterone-ADT group. Use of abiraterone alone adequately suppressed testosterone levels in 35/37 (94.6%) patients. Patients receiving abiraterone alone had a median PSA reduction of 80.2% versus 79.5% in patients receiving abiraterone plus ADT. The median PSA progression-free survival in patients receiving abiraterone alone was 27.4 versus 25.8 months in patients receiving abiraterone plus ADT (hazard ratio [HR] 1.10; 95% confidence interval [CI] 0.65-1.71; p = 0.82). In addition, abiraterone alone was associated with an overall survival of 3.6 versus 3.1 years in patients receiving abiraterone plus ADT (HR 0.90; 95% CI 0.50-1.62; p = 0.72). There were no differences in PFS or OS between groups after performing Cox multivariable regression analyses. CONCLUSION: Use of abiraterone alone was associated with comparable clinical outcomes to patients who received abiraterone together with ADT. Further prospective studies are warranted to evaluate the impact of abiraterone alone on treatment outcomes and cost savings.

Mental health care utilization among men with castration-resistant prostate cancer receiving abiraterone or enzalutamide.

BACKGROUND: Abiraterone and enzalutamide are castration-resistant prostate cancer (CRPC) therapies with potentially distinct associations with mental health symptoms given their differing antiandrogen targets. METHODS: We used national Veterans Health Administration data to identify patients with CRPC who received first-line abiraterone or enzalutamide from 2010 to 2017. Using Poisson regression, we compared outpatient mental health encounters per 100 patient-months on drug between the abiraterone and enzalutamide cohorts adjusting for patient factors (e.g., age). We compared mental health encounters in the year before versus after starting therapy using the McNemar test. RESULTS: We identified 2902 CRPC patients who received abiraterone (n = 1992) or enzalutamide (n = 910). We found no difference in outpatient mental health encounters between the two groups (adjusted incident rate ratio [aIRR] 1.04, 95% confidence interval [CI] 0.95-1.15). However, men with preexisting mental health diagnoses received 81.3% of the outpatient mental health encounters and had higher rates of these encounters with enzalutamide (aIRR 1.21, 95% CI 1.09-1.34). Among patients with ≥1 year of enrollment before and after starting abiraterone (n = 1139) or enzalutamide (n = 446), there was no difference in mental health care utilization before versus after starting treatment (17.0% of patients vs. 17.6%, p = 0.60, abiraterone; 16.4% vs. 18.4%, p = 0.26, enzalutamide). CONCLUSION: We found no overall differences in mental health care utilization between CRPC patients who received first-line abiraterone versus enzalutamide. However, men with preexisting mental health diagnoses received the majority of mental health care and had more mental health visits with enzalutamide.

Relationship of Ethinylestradiol/Drospirenone Prescription on Work Productivity and Activity Impairment Among Women With Menstruation-Related Symptoms: A Multicenter Prospective Observational Study.

OBJECTIVE: The aim of the study is to examine changes in work productivity and daily activity impairment among women by starting ethinylestradiol (EE)/drospirenone (DRSP) for perimenstrual symptoms. METHODS: Participants were women who were newly prescribed EE/DRSP at 25 gynecological clinics in Japan. Eligible participants recorded daily intake of EE/DRSP and the Work Productivity Activity Impairment Questionnaire General Health every 2 weeks for 3 months by smartphone app. A linear mixed-effects model was used to see changes in work productivity impairment and activity impairment relative to baseline. RESULTS: A total of 222 participants were eligible. Work productivity impairment recovered by 20.0% (95% confidence interval, 14.1%-26.0%) at 1 m and maintained for 2 months. Activity impairment recovered by 20.1% (95% confidence interval, 15.5%-24.7%) at 1 m and thereafter. CONCLUSIONS: Improvements in work productivity and daily activities were observed at 1 m after EE/DRSP initiation, with a sustained effect thereafter.

Predicting response to enzalutamide and abiraterone in metastatic prostate cancer using whole-omics machine learning.

Response to androgen receptor signaling inhibitors (ARSI) varies widely in metastatic castration resistant prostate cancer (mCRPC). To improve treatment guidance, biomarkers are needed. We use whole-genomics (WGS; n = 155) with matching whole-transcriptomics (WTS; n = 113) from biopsies of ARSI-treated mCRPC patients for unbiased discovery of biomarkers and development of machine learning-based prediction models. Tumor mutational burden (q < 0.001), structural variants (q < 0.05), tandem duplications (q < 0.05) and deletions (q < 0.05) are enriched in poor responders, coupled with distinct transcriptomic expression profiles. Validating various classification models predicting treatment duration with ARSI on our internal and external mCRPC cohort reveals two best-performing models, based on the combination of prior treatment information with either the four combined enriched genomic markers or with overall transcriptomic profiles. In conclusion, predictive models combining genomic, transcriptomic, and clinical data can predict response to ARSI in mCRPC patients and, with additional optimization and prospective validation, could improve treatment guidance.

Abiraterone-Docetaxel scheduling for metastatic castration-resistant prostate cancer based on evolutionary dynamics.

Patients with metastatic castration-resistant prostate cancer (mCRPC) are divided into three groups based on their response to Abiraterone treatment: best responder, responder, and non-responder. In the latter two groups, successful outcomes may not be achieved due to the development of drug-resistant cells in the tumor environment during treatment. To overcome this challenge, a secondary drug can be used to control the population of drug-resistant cells, potentially leading to a longer period of disease inhibition. This paper proposes using a combination of Docetaxel and Abiraterone in some polytherapy methods to control both the overall cancer cell population and the drug-resistant subpopulation. To investigate the competition and evolution of mCRPC cancer phenotypes, as in previous studies, the Evolutionary Game Theory (EGT) has been used as a mathematical modeling of evolutionary biology concepts.

Bayesian Machine Learning Enables Identification of Transcriptional Network Disruptions Associated with Drug-Resistant Prostate Cancer.

Survival rates of patients with metastatic castration-resistant prostate cancer (mCRPC) are low due to lack of response or acquired resistance to available therapies, such as abiraterone (Abi). A better understanding of the underlying molecular mechanisms is needed to identify effective targets to overcome resistance. Given the complexity of the transcriptional dynamics in cells, differential gene expression analysis of bulk transcriptomics data cannot provide sufficient detailed insights into resistance mechanisms. Incorporating network structures could overcome this limitation to provide a global and functional perspective of Abi resistance in mCRPC. Here, we developed TraRe, a computational method using sparse Bayesian models to examine phenotypically driven transcriptional mechanistic differences at three distinct levels: transcriptional networks, specific regulons, and individual transcription factors (TF). TraRe was applied to transcriptomic data from 46 patients with mCRPC with Abi-response clinical data and uncovered abrogated immune response transcriptional modules that showed strong differential regulation in Abi-responsive compared with Abi-resistant patients. These modules were replicated in an independent mCRPC study. Furthermore, key rewiring predictions and their associated TFs were experimentally validated in two prostate cancer cell lines with different Abi-resistance features. Among them, ELK3, MXD1, and MYB played a differential role in cell survival in Abi-sensitive and Abi-resistant cells. Moreover, ELK3 regulated cell migration capacity, which could have a direct impact on mCRPC. Collectively, these findings shed light on the underlying transcriptional mechanisms driving Abi response, demonstrating that TraRe is a promising tool for generating novel hypotheses based on identified transcriptional network disruptions. SIGNIFICANCE: The computational method TraRe built on Bayesian machine learning models for investigating transcriptional network structures shows that disruption of ELK3, MXD1, and MYB signaling cascades impacts abiraterone resistance in prostate cancer.

Molecular features and race-associated outcomes of SPOP-mutant metastatic castration-resistant prostate cancer.

BACKGROUND: Inactivating alterations in SPOP frequently occur in prostate cancer and promote increased dependency on androgen receptor (AR)-mediated oncogenic signaling. The presence of SPOP mutation (SPOP-mutant [SPOP-mut]) may therefore impact therapeutic outcomes with AR-directed therapies and docetaxel in metastatic castration-resistant (mCRPC). METHODS: This was a retrospective study of mCRPC patients treated at an urban academic hospital (n = 103). Patients underwent tumor DNA sequencing to determine SPOP mutational status (SPOP-mut). Outcomes measured were overall survival (OS) from diagnosis and treatment with second-generation AR signaling inhibitor (ARSI) or docetaxel and time to PSA progression (prostate-specific antigen-progression-free survival [PSA-PFS]) compared by SPOP status using Kaplan-Meier curves and log-rank test. The univariable and multivariable Cox proportional hazard model evaluated the association of SPOP mutation and outcomes adjusted for clinicopathologic features. RESULTS: SPOP-mut was associated with longer PSA-PFS in mCRPC (median 1.79 vs. 0.84 years; p = 0.06) and multivariate analysis (hazard ratio [HR] = 0.37; 95% confidence interval [CI]: 0.17-0.84; p = 0.02). SPOP-mut demonstrated a higher median PSA decline compared to SPOP wild-type (median decline 100% vs. 92%, p = 0.02). SPOP-mut was not associated with OS from the start of ARSI or docetaxel (median OS not reached vs. 2.0 years) or PSA-PFS on docetaxel (median PSA-PFS 0.4 vs. 0.5 years) in mCRPC. The majority of SPOP mutations were identified in African American (AA) patients (69.2%) compared to Caucasian patients (30.8%). Race-associated multivariate analysis revealed no significant differences in OS from the start of ARSI or the start of docetaxel and no differences in ARSI or docetaxel PSA-PFS between AA and Caucasian patients. Molecular profiling demonstrated that AA patients had a higher frequency of SPOP mutations and greater heterogeneity of SPOP variants within the coding sequence. Analysis of concurrent genomic alterations revealed that SPOP mutations co-occur with APC mutations (p = 0.001) and alterations in the Wnt pathway (p = 0.017). CONCLUSIONS: Inactivating mutations in SPOP are associated with better response to ARSI treatment in mCRPC overall. Additional analysis with a larger cohort is needed to evaluate the association of SPOP status and outcomes with docetaxel. Race-associated clinical outcomes and molecular features were observed, suggesting the benefit of biomarker-directed therapy selection for individualized patient subsets in guiding treatment decisions for mCRPC patients.

Qi Ling decoction enhances abiraterone treatment via suppression of autophagy in castration resistant prostate cancer.

Abiraterone acetate has exhibited impressive results in improving progression-free survival of patients with metastatic castration-resistant prostate cancer. However, many patients may develop abiraterone resistance with a variable duration of response. Hence, identifying a remedy to overcome abiraterone resistance is critical for patients with castration-resistant prostate cancer. In this study, we aim to explore the potential of Qi Ling decoction (QLD), a traditional Chinese medicine, in attenuating abiraterone resistance in prostate cancer. Cell viability and apoptosis were respectively measured by Cell Counting Kit-8 (CCK-8) assay and flow cytometry. The protein levels were assessed by Western blotting assay. Autophagosome formation was quantified by counting LC3 puncta. We found that QLD was capable of promoting abiraterone-induced apoptosis and cell death of PC3-AbiR and DU145-AbiR cells in vitro. A combination of QLD and abiraterone yielded a better tumor inhibition effect than QLD alone and abiraterone alone. Further investigation revealed that QLD restored the abiraterone sensitivity of PC3-AbiR and DU145-AbiR cells through modulating autophagy. These findings suggest that QLD might serve as a potential remedy to enhance the therapeutical effect of abiraterone for patients with castration-resistant prostate cancer.

Evaluation of Medicare Coverage and Estimated Out-of-Pocket Costs for Generic Abiraterone Products.

This cross-sectional study evaluates the association of generic competition and changes in product coverage and cost-sharing by using Medicare data and estimated out-of-pocket costs for the oral specialty drug abiraterone.

Pooled efficacy results of estetrol/drospirenone combined oral contraception phase 3 trials.

OBJECTIVE: To evaluate overall and subgroup efficacy of an estetrol (E4) 15 mg drospirenone (DRSP) 3 mg oral contraceptive in a 24/4-day regimen. STUDY DESIGN: We pooled efficacy outcomes from 2 pivotal phase 3 contraceptive trials with E4/DRSP conducted in the United States/Canada and Europe/Russia. We assessed Pearl Index (PI; pregnancies per 100 participant-years) and 13-cycle life-table pregnancy rates in at-risk cycles (confirmed intercourse and no other contraceptive use) among participants 16 to 35 years. We calculated PI by age and further subcategorization (contraceptive history and body mass index [BMI]). We performed multivariable analysis using Cox regression to assess impact of potential confounding factors. RESULTS: Analyses included 3027 participants, of whom 451 (14.9%) had a BMI ≥30 kg/m2. The pooled PI was 1.52 (95% confidence interval 1.04-2.16) and the 13-cycle life-table pregnancy rate was 1.28% (0.83%-1.73%). We calculated unadjusted pooled PI in participants 16 to 25 years and 26 to 35 years of 1.61 (0.94-2.57) and 1.43 (0.78-2.40), respectively; in new starters and switchers of 1.88 (1.09-3.00) and 1.24 (0.68-2.08), respectively; and by BMI <25 kg/m2, 25 to 29.9 kg/m2, and ≥30 kg/m2 of 1.14 (0.64-1.88), 2.19 (1.05-4.03), and 2.27 (0.83-4.94), respectively. In multivariable analysis, we found associations of prior pregnancy (hazard ratio [HR] 3.61[1.56-8.38]), Black race (HR 4.61[1.97-10.80]), age 16 to 25 years (HR 2.37[1.09-5.15]) and compliance <99% of expected pills (HR 4.21[2.04-8.66]) with conception. CONCLUSION: E4/DRSP is an effective oral contraceptive overall and across subgroups stratified by age, contraceptive history, and BMI. Other than compliance, predictors of contraceptive failure are nonmodifiable. IMPLICATIONS STATEMENT: Pooled results from two phase 3 trials demonstrate high contraceptive efficacy of the novel estetrol-drospirenone oral contraceptive. Several non-modifiable risk factors, including prior pregnancy, race, and age, are associated with higher pregnancy risk. Additional research is needed to better understand predictors of combined oral contraceptive failure.

Serum prolactin level as a predictive factor for abiraterone response in patients with metastatic castration-resistant prostate cancer.

BACKGROUND: To investigate the prognostic value and potential therapeutic target of the baseline serum hormones in patients with metastatic castration-resistant prostate cancer (mCRPC) treated with abiraterone. METHODS: This retrospective study was performed in patients with mCRPC receiving abiraterone acetate (AA) from July 2016 to September 2020. Patients who had serum hormone tests within 2 weeks before AA treatment were included. Univariate analysis and Cox regression were performed to evaluate the correlation of sex hormones with progression-free survival (PFS) and overall survival (OS). Prolactin (PRL) expression in the clinical specimens was evaluated by immunohistochemistry. Bone metastases were quantified by automated Bone Scan Index (aBSI). RESULTS: The study included 61 patients with a median follow-up of 19.0 months. Patients with lower baseline PRL levels (median) responded better to AA than those with higher baseline PRL levels as indicated by prostate-specific antigen (PSA) reduction (PSA90, 66.7% vs. 25.8%, p = 0.001), PFS (19.6 vs. 7.9 months), and OS (52.8 vs. 19.2 months). Cox regression adjusted for clinical factors also confirmed that baseline PRL level was an independent predictive factor for PFS (hazard ratio = 1.096, p = 0.007). Prostatic PRL expression increased as the disease progressed. PRL expression was also detected in biopsy samples from bone metastasis but not in normal bone tissue, and the serum PRL levels were positively correlated with aBSIs (r = 0.28, p = 0.037). CONCLUSIONS: Serum PRL levels are predictive of response to AA in patients with mCRPC. Serum PRL levels are positively correlated with the volume of metastatic bone disease.

Study protocol and preliminary results from a mono-centric cohort within a trial testing stereotactic body radiotherapy and abiraterone (ARTO-NCT03449719).

BACKGROUND: ARTO trial was designed to evaluate the difference in terms of outcomes between patients affected by oligo metastatic castrate resistant prostate cancer (mCRPC) treated with Abiraterone acetate and randomized to receive or not SBRT on all sites of disease. Here, we present a preliminary analysis conducted on patients enrolled at promoting institution. OBJECTIVE: To present a preliminary overview about population features, clinical outcomes, adverse events, quality of life and explorative translational research. DESIGN, SETTING, AND PARTICIPANTS: ARTO (NCT03449719) is a phase II trial including patients affected by oligo mCRPC, randomized to receive standard of care (GnRH agonist or antagonist plus abiraterone acetate 1000 mg and oral prednisone 10 mg daily) with or without SBRT on all metastatic sites of disease. All subjects have < 3 bone or nodal metastases. All patients are treated in I line mCRPC setting, no previous lines of treatment for mCRPC are allowed. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Data about a mono-centric cohort of 42 patients enrolled are presented in the current analysis, with focus on baseline population features, PSA drop at 3 months, biochemical response, and quality of life outcomes. Descriptive statistics regarding translational research are also presented. RESULTS AND LIMITATION: Significant difference in terms of PSA drop at three months was not detected (p = 0.68). Biochemical response (PSA reduction > 50%) was reported in 73.7 versus 76.5% of patients in control vs SBRT arm, respectively (p = 0.84). All patients are alive. Progression occurred in 1 versus 0 patients in the control versus SBRT arm, respectively. After 3 months, an average decrease of 13 points in terms of Global Health Score was reported for the overall population. However, complete recovery was noticed at 6 months. Circulating tumor cells detection rate was 40%. CONCLUSIONS: SBRT + Abiraterone treatment was safe and well tolerated, non-significant trend in terms of PSA drop and biochemical response at 3 months was detected in SBRT arm. Interestingly, CTCs detection in this selected cohort of oligo-mCRPC was lower if compared to historical data of unselected mCRPC patients.

Abiraterone switches castration-resistant prostate cancer dependency from adrenal androgens towards androgen receptor variants and glucocorticoid receptor signalling.

INTRODUCTION: Castration-resistant prostate cancer (CRPC) remains dependent on androgen receptor (AR) signalling, which is largely driven by conversion of adrenal androgen precursors lasting after castration. Abiraterone, an inhibitor of the steroidogenic enzyme CYP17A1, has been demonstrated to reduce adrenal androgen synthesis and prolong CRPC patient survival. To study mechanisms of resistance to castration and abiraterone, we created coculture models using human prostate and adrenal tumours. MATERIALS AND METHODS: Castration-naïve and CRPC clones of VCaP were incubated with steroid substrates or cocultured with human adrenal cells (H295R) and treated with abiraterone or the antiandrogen enzalutamide. Male mice bearing VCaP xenografts with and without concurrent H295R xenografts were castrated and treated with placebo or abiraterone. Response was assessed by tumour growth and PSA release. Plasma and tumour steroid levels were assessed by LC/MS-MS. Quantitative polymerase chain reaction determined steroidogenic enzyme, nuclear receptor and AR target gene expression. RESULTS: In vitro, adrenal androgens induced castration-naïve and CRPC cell growth, while precursors steroids for de novo synthesis did not. In a coculture system, abiraterone blocked H295R-induced growth of VCaP cells. In vivo, H295R promoted castration-resistant VCaP growth. Abiraterone only inhibited VCaP growth or PSA production in the presence of H295R. Plasma steroid levels demonstrated CYP17A1 inhibition by abiraterone, whilst CRPC tumour tissue steroid levels showed no evidence of de novo intratumoural androgen production. Castration-resistant and abiraterone-resistant VCaP tumours had increased levels of AR, AR variants and glucocorticoid receptor (GR) resulting in equal AR target gene expression levels compared to noncastrate tumours. CONCLUSIONS: In our model, ligand-dependent AR-regulated regrowth of CRPC was predominantly supported via adrenal androgen precursor production while there was no evidence for intratumoural androgen synthesis. Abiraterone-resistant tumours relied on AR overexpression, expression of ligand-independent AR variants and GR signalling.

Outcomes Among African American and Non-Hispanic White Men With Metastatic Castration-Resistant Prostate Cancer With First-Line Abiraterone.

Importance: Prospective evidence suggests abiraterone is associated with superior progression-free survival for African American men compared with non-Hispanic White men with metastatic castration-resistant prostate cancer (mCRPC). Objective: To investigate differences in outcomes with first-line abiraterone therapy between African American and non-Hispanic White men with mCRPC in a national real-world cohort. Design, Setting, and Participants: This retrospective cohort study used a nationwide electronic health record-derived database of 3808 men receiving first-line therapy for mCRPC between January 1, 2012, and December 31, 2018. Data analysis was performed between January 1, 2020, and June 1, 2021. Median follow-up was 13 months (IQR, 7-22 months). Propensity score-based inverse probability of treatment weighting was applied to reduce imbalance in measured confounders between patients receiving first-line abiraterone vs other first-line therapies. Deidentified patient data originated from a geographically diverse set of approximately 280 cancer clinics (approximately 800 sites of care) throughout the United States. Participants had newly diagnosed mCRPC and were receiving first-line systemic therapy during the study period. Exposures: Receipt of abiraterone for first-line therapy. Main Outcomes and Measures: Overall survival from start of first-line treatment. Stratified analyses investigated overall survival within each race group, with first-line enzalutamide as the comparator. Results: Among 3808 patients with mCRPC, there were 2615 non-Hispanic White men (68.7%; mean [SD] age at diagnosis, 74 [8] years) and 404 African American men (10.6%; mean [SD] age at diagnosis, 69 [9] years), and 1729 patients (45.4%) in the cohort received first-line abiraterone. Among patients receiving first-line abiraterone, African American men had higher median overall survival than non-Hispanic White men (23 months [IQR, 10-37 months] vs 17 months [IQR, 9-32 months], respectively; inverse probability of treatment weighting hazard ratio, 0.76; 95% CI, 0.60-0.98). A race-by-treatment interaction existed for first-line abiraterone vs first-line enzalutamide (hazard ratio for abiraterone vs enzalutamide: non-Hispanic White men, 1.21 [95% CI, 1.06-1.38]; African American men, 1.05 [95% CI, 0.74-1.50]; interaction P = .02). There was no overall survival difference between first-line abiraterone and first-line enzalutamide among African American patients (24 vs 24 months, respectively; inverse probability of treatment weighting hazard ratio, 1.05; 95% CI, 0.74-1.50). First-line abiraterone was associated with decreased median overall survival relative to first-line enzalutamide among non-Hispanic White patients (17 months [IQR, 9-32 months] vs 20 months [IQR, 10-36 months], respectively; inverse probability of treatment weighting hazard ratio, 1.21; 95% CI, 1.06-1.38). Conclusions and Relevance: In this cohort study of patients who received first-line systemic therapy for mCRPC, African American men who received abiraterone had improved overall survival compared with non-Hispanic White men. Future prospective studies should assess drivers of differential abiraterone outcomes in mCRPC between African American and non-Hispanic White men, including differences in genetic factors and socioeconomic status, to inform treatment strategies.