Background: Improved clinical outcomes have been observed in patients with metastatic castration-sensitive prostate cancer (mCSPC) who experience deep prostate-specific antigen (PSA) responses after treatment with androgen receptor pathway inhibitors (ARPIs). Objective: This retrospective longitudinal study aimed to compare real-world PSA90 response (≥90% reduction from pretreatment levels) in Black patients with mCSPC treated with apalutamide vs abiraterone acetate. Methods: Electronic medical record (EMR) data from Precision Point Specialty Analytics were linked to claims data from the Komodo Research Database. Black adult patients with mCSPC who initiated apalutamide or abiraterone acetate on or after 9/17/2019 were included. Inverse probability of treatment weighting was used to balance patient characteristics between treatment cohorts. PSA90 was evaluated during the on-treatment period, defined as the time from index date to the earliest of treatment discontinuation, initiation of a new ARPI or radiopharmaceutical, or end of insurance claims activity or clinical activity. Weighted Kaplan-Meier curves and hazard ratios (HRs) were used to compare PSA90 responses between treatment cohorts. Results: This study included 363 patients, of which 236 initiated apalutamide and 127 initiated abiraterone acetate. At 6 months following treatment initiation, a greater proportion of patients treated with apalutamide (65.4%) vs abiraterone acetate (49.0%) achieved a PSA90 response. Patients who initiated apalutamide vs abiraterone acetate were 66% more likely to achieve a PSA90 response within 6 months of treatment initiation (HR, 1.66; 95% confidence interval, 1.18-2.35; P = .004). The median time-to-PSA90 response was approximately 6 months earlier for patients treated with apalutamide (3.3 months) compared with abiraterone acetate (9.1 months). Discussion: This study leveraged robust information from combined insurance claims and routinely collected EMR data to evaluate PSA90, a clinically relevant biomarker of treatment response, among Black patients with mCSPC. These results are among the first in this understudied patient population and suggest that a deeper and earlier PSA response achieved with apalutamide relative to abiraterone acetate can extend to Black patients in a real-world US clinical setting. Conclusion: Black patients treated with apalutamide experienced significantly higher PSA90 response rates than those treated with abiraterone acetate, suggesting possible clinical benefits from early treatment response in this population.

BackgroundImproved clinical outcomes have been observed in patients with metastatic castration-sensitive prostate cancer (mCSPC) who experience deep prostate-specific antigen (PSA) responses after treatment with androgen receptor pathway inhibitors (ARPIs).ObjectiveThis retrospective longitudinal study aimed to compare real-world PSA90 response (≥90% reduction from pretreatment levels) in Black patients with mCSPC treated with apalutamide vs abiraterone acetate.MethodsElectronic medical record (EMR) data from Precision Point Specialty Analytics were linked to claims data from the Komodo Research Database. Black adult patients with mCSPC who initiated apalutamide or abiraterone acetate on or after 9/17/2019 were included. Inverse probability of treatment weighting was used to balance patient characteristics between treatment cohorts. PSA90 was evaluated during the on-treatment period, defined as the time from index date to the earliest of treatment discontinuation, initiation of a new ARPI or radiopharmaceutical, or end of insurance claims activity or clinical activity. Weighted Kaplan-Meier curves and hazard ratios (HRs) were used to compare PSA90 responses between treatment cohorts.ResultsThis study included 363 patients, of which 236 initiated apalutamide and 127 initiated abiraterone acetate. At 6 months following treatment initiation, a greater proportion of patients treated with apalutamide (65.4%) vs abiraterone acetate (49.0%) achieved a PSA90 response. Patients who initiated apalutamide vs abiraterone acetate were 66% more likely to achieve a PSA90 response within 6 months of treatment initiation (HR, 1.66; 95% confidence interval, 1.18-2.35; P = .004). The median time-to-PSA90 response was approximately 6 months earlier for patients treated with apalutamide (3.3 months) compared with abiraterone acetate (9.1 months).DiscussionThis study leveraged robust information from combined insurance claims and routinely collected EMR data to evaluate PSA90, a clinically relevant biomarker of treatment response, among Black patients with mCSPC. These results are among the first in this understudied patient population and suggest that a deeper and earlier PSA response achieved with apalutamide relative to abiraterone acetate can extend to Black patients in a real-world US clinical setting.ConclusionBlack patients treated with apalutamide experienced significantly higher PSA90 response rates than those treated with abiraterone acetate, suggesting possible clinical benefits from early treatment response in this population.

Purpose: Docetaxel and Abiraterone acetate are the drugs of choice, especially for cases of prostate cancer that are insensitive to androgen deprivation therapy. Nrf2, which has antioxidative properties in normal cells, also protects cancer cells from apoptosis, causing the cells to be unresponsive to treatment. This study aimed to investigate the effect of Docetaxel and Abiraterone acetate administration to human prostate cancer cells on Nrf2 expression in vitro. Materials and Methods: Two different prostate cancer cell lines were used: androgen-responsive and non-androgen-responsive. 4 groups were formed as control, AA (Abiraterone Acetate), DTX (Docetaxel), and AA+DTX. Cells were cultured with abiraterone acetate and Docetaxel for 72 hours. Then, Nrf2 expression changes were examined by immunofluorescence and Western blot methods. Results: In LNCaP cells, Nrf2 was decreased in DTX and DTX+AA groups compared to the control and AA groups. Nrf2 was the same between Control and AA groups. In PC3 cells, Nrf2 was higher in AA and AA+DTX groups compared to Control and DTX groups. Nrf2 expressions of the Control and DTX groups were similar. Conclusion: Expression changes of Nrf2 protein were observed in both cell lines. It has been predicted that Docetaxel may increase chemotherapeutic efficacy by suppressing Nrf2 expression in androgen-sensitive prostate cancer cells and may reduce mortality rates in cancer patients. In androgen-insensitive cells, it has been predicted that Abiraterone acetate application may increase Nrf2 expression and decrease the effectiveness of treatment by developing resistance to drugs.

The management of metastatic castration-resistant prostate cancer (mCRPC) following progression on androgen deprivation therapy (ADT) combined with androgen receptor pathway inhibitors (ARPI) in the castration-sensitive (CS) setting remains unclear. Limited data exist comparing the efficacy of ARPI versus docetaxel as first-line treatment in this context. We conducted a retrospective multicentre study across three tertiary cancer centres in Saudi Arabia, including 60 patients with pathologically confirmed mCRPC who progressed after doublet therapy (ADT + ARPI) in the CS setting between January 2018 and September 2022. Patients received either ARPI (abiraterone acetate or enzalutamide) or docetaxel as first-line therapy for mCRPC. Primary endpoints were prostate-specific antigen (PSA) response rate and biochemical progression-free survival (PFS). Secondary endpoints included overall survival (OS) and treatment patterns. PSA response was defined as ≥ 30% decline at 12 weeks from baseline. Survival analyses were performed using Kaplan-Meier and log-rank tests. Among 60 eligible patients (median age 65 years), 28 received ARPI and 32 received docetaxel. PSA response rates were 39.3% for ARPI and 37.5% for docetaxel. Median PFS was 2.9 months (95% CI 0.37-5.5) for ARPI and 4.5 months (95% CI 2.6-6.3) for docetaxel (p = 0.137). Median OS was 13 months (95% CI 4.0-23.9) for ARPI and 16 months (95% CI 6.1-25.9) for docetaxel (p = 0.236). In patients with visceral metastases, docetaxel conferred significantly longer OS compared to ARPI (14.4 vs. 5.9 months, p = 0.025). Multivariate analysis identified nadir PSA in the CS setting as a predictor of PFS and first-line therapy in the CR setting, visceral metastasis and duration of therapy in CS setting as predictors of OS. In patients progressing to mCRPC after doublet therapy in the CS setting, docetaxel demonstrated a trend toward longer PFS and OS compared to ARPI, with a significant survival advantage in those with visceral metastases. These findings highlight the need for prospective randomized trials and biomarker-driven treatment strategies to optimize therapy sequencing in this evolving treatment landscape.

To accelerate prostate cancer drug development and identification of promising therapies, we aimed to establish a framework for a multi-modal therapy (MMT) approach using intermediate endpoints of efficacy due to treatment. In the MetaCURE trial, patients with untreated, high-risk localized (cohort A) or low-volume metastatic (cohort B) disease were randomized 1:1 to apalutamide or apalutamide and abiraterone acetate plus prednisone, and androgen deprivation therapy for 10 months. Cohort B also received stereotactic body radiotherapy at 4 months. All patients underwent a radical prostatectomy (6 months +/- postoperative radiotherapy at 10 months). The primary endpoint was pathologic complete response (pCR; no residual tumor) or minimal residual disease (MRD; ≤5 mm residual carcinoma), and the secondary endpoint an undetectable prostate-specific antigen (PSA) following testosterone (T) recovery (T ≥150 ng/dl) at 24 months. A pCR or MRD was achieved in 4 (12%; 90% CI: 4%-26%) and 5 (15%; 90% CI 6%-29%) patients in cohorts A and B respectively. Undetectable PSA and T recovery at 24 months occurred in 20 (61%; 95% CI:42%-77%) patients in cohort A and 13 (39%; 95% CI: 23%-58%) in cohort B. MMT for newly diagnosed high-risk localized and low-volume metastatic PC is feasible, safe, and provides a rapid readout of efficacy. A significant proportion of patients, including those with oligometastatic disease maintained an undetectable PSA following T recovery at the 2-years. These results have informed the design of an adaptive trial using MMT on a continuous basis to prioritize effective approaches for further study.

Castration-resistant prostate cancer(CRPC) continues to represent a critical therapeutic hurdle owing to its resistance to both androgen deprivation and next-generation antiandrogens like abiraterone (ABI). One of the key mechanisms underlying this resistance involves overexpression of aldo-keto reductase 1C3 (AKR1C3), an enzyme contributing to intratumoral androgen biosynthesis. In this study, casticin (CAS), a flavonoid derived from Vitex agnus-castus, was identified as a potent inhibitor of AKR1C3. CAS showed potent inhibitory activity in enzymatic assays (IC₅₀ = 5.99 µM), significantly suppressed AKR1C3-mediated coumberone metabolism in 22Rv1 prostate cancer cells, and showed greater cytotoxicity in AKR1C3-expressing 22Rv1 cells relative to AKR1C3-deficient LNCaP cells. CAS significantly enhanced ABI's cytotoxic efficacy in 22Rv1 cells, as evidenced by synergistic interactions (CI: 0.31-0.71); however, no such synergy was observed in LNCaP cells or with enzalutamide. CAS enhanced apoptosis in ABI-treated 22Rv1 cells, as well as combination showed only a limited effect against normal epithelial PNT-2 cell line. Docking and molecular dynamics simulations indicated a stable CAS-AKR1C3 interaction, characterized by crucial hydrogen bonding and aromatic stacking within the active site. These results suggest that CAS is a promising chemosensitizer targeting AKR1C3 to overcome ABI resistance in CRPC.

IntroductionAbiraterone acetate is a key therapeutic agent for castration-resistant prostate cancer (CRPC), but the cancer resistance limits its long-term efficacy. While several mechanisms of abiraterone acetate resistance have been proposed, the role of microRNAs (miRNAs) in this process remains incompletely understood. Here the aim of the study was to investigate miR-143 as a potential tumor suppressor in prostate cancer, and elucidate its involvement in abiraterone acetate resistance. Additionally, Qiling decoction (QLD), a traditional Chinese medicine formulation, was tested for its ability to restore miR-143 expression and enhance abiraterone efficacy.MethodsAbiraterone acetate-resistant prostate cancer (PC) cell lines, PC3-AbiR and DU145-AbiR, were established through long-term abiraterone exposure. The expression of miR-143 was analyzed using qRT-PCR, and its effects on the JNK/p-Bcl2-Beclin1 signaling axis were examined via Western blot and co-immunoprecipitation assays. Functional experiments, including CCK-8 assays, were carried out to evaluate how miR-143 modulation affects abiraterone acetate sensitivity.ResultsmiR-143 expression was significantly downregulated in abiraterone acetate-resistant PC cells. Downregulation of miR-143 was shown to be linked with increased phosphorylation of JNK and p-Bcl2, along with elevated expression of Beclin1, indicating activation of the JNK/p-Bcl2-Beclin1 signaling axis. Functional studies revealed that miR-143 inhibition promoted cell survival and autophagy, while its overexpression restored abiraterone acetate sensitivity. Treatment with QLD upregulated miR-143 expression, suppressed JNK/p-Bcl2-Beclin1 signaling, and enhanced abiraterone acetate-induced cytotoxicity. Inhibition of miR-143 abolished the effects of QLD, confirming its central role in mediating abiraterone acetate resistance. These findings demonstrate that miR-143 downregulation contributes to abiraterone acetate resistance in prostate cancer by activating the JNK/p-Bcl2-Beclin1 signaling axis and promoting autophagy.ConclusionRestoration of miR-143 expression through QLD treatment enhances abiraterone acetate sensitivity, suggesting a potential therapeutic strategy for overcoming drug resistance in CRPC.

Prostate cancer (PCa) is a leading malignancy among men, with treatment resistance posing significant clinical challenges, especially in advanced, castration-resistant cases. Abiraterone acetate (AA), a CYP17A1 inhibitor, suppresses androgen biosynthesis and is used to manage metastatic disease; however, its complete mechanism of action is not fully understood. This study investigates whether AA modulates androgen receptor (AR) expression via endoplasmic reticulum (ER) stress in PCa. LNCaP (androgen-sensitive) and 22Rv1 (AR-variant-expressing) PCa cells were treated with AA (0.5-16 μM) for 24-72 h. Cytotoxicity and proliferation were assessed via CCK-8 and BrdU assays. Apoptosis was quantified by caspase-3/7 activation. ER stress markers (PERK, ATF4, CHOP) and AR were evaluated using RT-qPCR, Western blot, and immunofluorescence staining. Pharmacological PERK inhibition (GSK2656157) and activation (CCT020312) validated pathway involvement. AA induced concentration/time-dependent cytotoxicity in LNCaP cells (24 h IC₅₀ = 4.8 μM) and 22Rv1 cells (24 h IC₅₀ = 15.2 μM) and proliferation decreased by 54.1% and 7.3% at 4.8 μM, respectively. AA triggered apoptosis in LNCaP cells, increasing caspase-3/7-positive cells to 71.58% vs. 1.73% in controls (p < 0.0001). Mechanistically, AA upregulated PERK, ATF4, and CHOP mRNA/protein (p < 0.0001) while downregulating AR. Immunofluorescence confirmed reciprocal ATF4 nuclear accumulation and AR reduction in AA-treated LNCaP cells. PERK inhibition reversed AA-induced effects, while PERK activation phenocopied AA's AR suppression and cytotoxicity, confirming ER stress mediation via the PERK/ATF4/CHOP axis. AA induces ER stress, leading to transcriptional downregulation of the AR and suppression of PCa cell viability and proliferation. Targeting the PERK pathway may enhance AA efficacy in AR-driven PCa.

Steroidal scaffolds, owing to their inherent structural rigidity, membrane permeability, and receptor affinity, have emerged as a critical class of molecules in anticancer drug development. This manuscript comprehensively explores the development, FDA-approved drugs such as dexamethasone, prednisone, and abiraterone acetate, synthetic innovations, and clinical potential of steroidal derivatives in anticancer therapy. Glucocorticoids and hormone modulators remain foundational in treating hematologic- and hormone-dependent cancers. At the same time, recent synthetic hybrids, including triazoles, isatins, pyrimidines, and benzisoselenazolones, have shown enhanced potency and selectivity across solid tumor models. The paper underscores the integration of steroids with potential anticancer activity, kinase inhibitors, and bioactive heterocycles to overcome pharmacokinetic limitations and hormone resistance. Several novel steroidal derivatives have demonstrated potent anticancer activity, as evidenced by low IC50 values: compound 29 (0.34µM), 30 (0.25µM and 0.28µM), 32 (0.00083, 0.029, and 0.056µM), and 36 (0.34µM). These findings underscore their strong cytotoxic potential against cancer cell lines. The central perspective emphasizes the resurgence of steroid-based drug design in the precision medicine era, especially in the context of emerging synthetic strategies and their translational viability in resistant and metastatic cancer phenotypes. Furthermore, several investigational steroid-drug combinations are currently being evaluated in clinical trials for advanced-stage cancers, including prostate, breast, and head and neck malignancies, underscoring their translational potential. This review highlights both the therapeutic promise and future directions of steroidal anticancer agent, reinforcing their value as a cornerstone in the development of targeted and supportive cancer therapy.

490MO Niraparib (NIRA) and abiraterone acetate plus prednisone (AAP) in Chinese patients with breast cancer susceptibility gene (BRCA) altered metastatic castration-sensitive prostate cancer (mCSPC): Subgroup analysis of the phase III AMPLITUDE trial

BONENAVI is a software designed to automatically calculate the automated bone scan index (aBSI) and quantify the number of bone metastases on bone scans. We conducted an investigator-initiated prospective study using BONENAVI to evaluate its prognostic utility for metastatic castration-sensitive prostate cancer (mCSPC). Eligible patients were assigned to one of two treatment groups: androgen deprivation therapy (ADT) combined with abiraterone acetate and prednisolone (AA group) or ADT alone (ADT group). The primary objective was to evaluate the prognostic value of the median aBSI in predicting progression-free survival (PFS) in the AA group. Secondary objectives included assessing the prognostic value of the median aBSI for PFS across all patients and the ADT group, as well as evaluating the prognostic utility of the aCHAARTED classifications based on BONENAVI. The median aBSI was not significantly associated with PFS in the AA group, the ADT group, or the overall patient cohort. Patients with aCHAARTED high-volume disease (HVD) exhibited worse PFS than those with low-volume disease (LVD) in the overall cohort and AA group; however, these differences were not statistically significant. In contrast, patients with aCHAARTED HVD in the ADT group had significantly worse PFS than those with LVD. The median aBSI could not predict the prognosis of patients with mCSPC. However, the aCHAARTED classification derived from BONENAVI may provide valuable insights for predicting PFS in patients with mCSPC undergoing ADT.

IntroductionBrazil’s Unified Health System (SUS) ensures universal and free healthcare access. However, when technologies are unavailable in this system, users can appeal to the courts. To support such decisions, the National Council of Justice established technical support centers that provide technical-scientific reports (TRs) to evaluate health technologies. This study aimed to analyze these TRs and rank the most judicialized health conditions.MethodsThis descriptive cross-sectional study was conducted at the Center of Health Technology Assessment, Hospital Sírio-Libanês, São Paulo-SP, Brazil, using the TRs available in the e-NATJus system (https://www.pje.jus.br/e-natjus/pesquisaPublica.php). The sample was limited to TRs published between 3 December 2018 and 12 November 2024. Quantitative analyses were summarized as percentages.ResultsOver 235,000 TRs were analyzed, with requests rising from 1,004 in 2019 to 71,120 in 2024. Medications represented 56.1 percent of TR demands, and 56.5 percent of the requested technologies were available in SUS. Favorable rulings occurred in 50.5 percent of cases. The most judicialized conditions were autism spectrum disorder (ASD), insulin-dependent diabetes, non-insulin-dependent diabetes, prostate cancer, and diabetic retinopathy. The main requests for ASD were aripiprazole, cannabis derivates, and applied behavior analysis therapy. Insulin glargine was the most requested drug for insulin-dependent diabetes, dapagliflozin for non-insulin-dependent diabetes, abiraterone acetate for prostate cancer, and ranibizumab for diabetic retinopathy.ConclusionsThe surge in TRs highlights growing demand for innovative treatments, many of which are unavailable in the SUS or lack robust evidence. Access challenges persist even for included therapies, emphasizing the need for equitable access and reliable evidence to guide decisions.

518eP Radiotherapy combined with fluzopanib and abiraterone acetate tablets (II) treatment for mCRPC

Low-dose abiraterone acetate for the treatment of prostate cancer: An observational cohort study.

Abiraterone (Abi) acetate, an anticancer drug, produces metabolites in the serum of patients with prostate cancer. Three unknown metabolites of Abi are previously discovered and the structures of two of these compounds are determined by comparing their LC‐based retention times with those of synthesized compounds. However, the structure of the third metabolite is not identified. Herein, two new Abi derivatives, 5α‐Δ1‐abiraterone (5α‐D1A) and 5β‐Δ1‐abiraterone (5β‐D1A), with a molecular weight of 348, are successfully synthesized as candidates for the third unknown metabolite. 5β‐D1A is confirmed as this third metabolite based on its retention time in the extracted ion chromatogram. The metabolic pathway may have formed 5β‐D1A rather than 5α‐D1A because of the higher activity of steroid 5β‐reductase compared with that of 5α‐reductase. These findings are expected to lead to the discovery of new metabolic pathways.

Patient-reported Outcomes for Men with Metastatic Castration-resistant Prostate Cancer Who Received Olaparib plus Abiraterone Versus Placebo plus Abiraterone in the Phase 3 PROpel Study.

This study evaluates the impact of early modification of upfront androgen receptor signaling inhibitors (ARSI) on outcomes among patients with metastatic hormone-sensitive prostate cancer (mHSPC). This retrospective, multicenter cohort study included 590 patients with mHSPC who received upfront ARSI combined with androgen deprivation therapy. All had a follow-up duration of ≥ 6 months. The impact of early modification of ARSI without progression on survival outcomes was analyzed. The inverse probability of treatment weighting (IPTW) was applied to adjust for confounding factors associated with survival outcomes, comparing patients who did and did not discontinue ARSI early. Upfront abiraterone acetate, apalutamide, and enzalutamide were used in 50.8%, 28.1%, and 21.0% of patients, respectively. The rates of withdrawal of the upfront ARSI and initial dose reduction were 21.2% and 6.1%, respectively. The highest withdrawal rate (33.1%) was with apalutamide, mainly due to adverse events (89.1%). Apalutamide use (odds ratio [OR] 2.39, 95% CI: 1.50-3.80) and a low-risk CHAARTED status (OR 1.84, 95% CI: 1.08-3.14) were identified as independent risk factors for early ARSI withdrawal. IPTW analysis revealed early ARSI withdrawal (within 6 months) significantly correlated with poor castration-resistant prostate cancer-free survival (CRPC-FS) (p = 0.004) and second progression-free survival (PFS2) (p = 0.035). However, it had no significant relationship with overall survival (p = 0.280). Early withdrawal of initial upfront ARSI was associated with poor CRPC-FS and PFS2 among mHSPC patients. Maximizing the effectiveness of first-line treatment requires optimal management of ARSI therapy. jRCTs021180021.

Canada’s Drug Agency (CDA-AMC) recommends that Nubeqa be reimbursed by public drug plans for use in combination with androgen deprivation therapy (ADT) for the treatment of metastatic castration-sensitive prostate cancer (mCSPC) if certain conditions are met. A subcommittee of the pan-Canadian Oncology Drug Review Expert Review Committee (pERC) determined that Nubeqa plus ADT demonstrates acceptable clinical value versus other androgen receptor pathway inhibitors (ARPIs) plus ADT in patients with mCSPC. This determination was sufficient for the pERC subcommittee to recommend that Nubeqa plus ADT be reimbursed. Given that Nubeqa is expected to be an alternative to other ARPI plus ADT regimens, acceptable clinical value refers to at least comparable value versus apalutamide plus ADT, enzalutamide plus ADT, and abiraterone acetate and prednisone plus ADT. Evidence from a pivotal phase III clinical trial demonstrated that darolutamide plus ADT resulted in clinically meaningful improvements compared with placebo plus ADT in outcomes that are relevant for the management of mCSPC, including time to progression to more advance disease. Although limited by imprecision, evidence from an indirect comparison suggested similar effects for darolutamide plus ADT versus the other ARPI plus ADT regimens. Nubeqa should only be covered for patients who currently meet the eligibility criteria used by each of the public drug plans for the other ARPI plus ADT regimens used in the treatment of mCSPC.

The choice of first line hormonal therapy in metastatic hormone-sensitive prostate cancer (mHSPC) is often based on comorbidities or physician preference due to the lack of data comparing abiraterone and enzalutamide in clinical trials and in clinical practice settings, especially in African American patients. To compare clinical outcomes in patients with mHSPC treated with abiraterone acetate or enzalutamide. This cohort study included all patients with mHSPC diagnoses in the US Veterans Affairs Health Care system who initiated abiraterone or enzalutamide between July 2017 and April 2023. Data were analyzed from April 2024 to March 2025. Receipt of abiraterone acetate or enzalutamide. Drug outcomes were established by estimating rates of tumor growth (g-rates) using prostate-specific antigen (PSA) values while receiving therapy and measuring overall survival (OS). Two different matching analyses were performed: inverse probability weighting (IPW) and 1:1 exact matching. A total of 1258 patients (median [IQR] age, 73 [69-79] years; 314 [25.0%] African American, 857 [68.1%] White, and 87 [6.9%] with other or unknown race) who received abiraterone and 311 patients (median [IQR] age, 74 [69-79] years; 84 [27.0%] African American, 207 [66.6%] White, and 20 [6.4%] with other or unknown race) who received enzalutamide were included. In the unweighted analysis, the abiraterone cohort had median (IQR) g-rate of 0.000137/d (0.000094-0.001519) and the enzalutamide cohort, 0.000137/d (0.000098-0.001815); median (IQR) OS was 36.2 (32.8-38.8) months for abiraterone and 36.2 (34.1-40.5) months for enzalutamide, with a median (IQR) follow-up of 28.7 (15.6-45.6) and 30.8 (16.1-39.1) months, respectively. In IPW analysis, using abiraterone as reference, the weighted median OS was comparable between abiraterone and enzalutamide in the full cohort (36.2; 95% CI, 32.8-38.8 vs 35.5; 95 % CI, 32.9-40.4 months; hazard ratio [HR], 1.09; 95% CI, 0.92-1.30; P = .32), African American veterans (39.7; 95% CI, 34.3-46.6 vs 40.3; 95% CI, 34.3-not reached months; HR, 0.98; 95% CI, 0.72-1.34; P = .90) and those with cardiovascular disease (31.5; 95% CI, 28.1-35.5 vs 35.0; 95% CI, 30.7-38.9; HR, 1.12; 95% CI, 0.91-1.37; P = .30). In 1:1 matched analysis, both the abiraterone and enzalutamide groups had 279 patients with 63 (23%) who were African American; these patients had a median (IQR) follow-up of 27.3 (15.3-40.8) and 31.1 (16.8-39.9) months, respectively. The 1:1 matched cohort consisted of 158 patients (57%) in each group with an initial Gleason score of 8 or higher, and 224 patients (80%) in each group with a PSA value of 50 ng/mL or higher at treatment initiation. For the 1:1 matched cohort and its subgroups of African American patients, patients with Gleason scores of 8 or higher, and patients with a starting PSA level of 50 ng/mL or higher, no statistically significant difference in median g-rate and OS was observed. This cohort study found that abiraterone and enzalutamide had comparable outcomes in a first-line mHSPC setting, with similar g-rates and OS in both White and African American patients. There were no differences in survival or g-rate between treatment based on race, comorbidities, and prostate cancer features, including Gleason score, PSA, and volume of disease.

Matching-Adjusted Indirect Comparisons (MAICs) of Talazoparib Plus Enzalutamide (TALA+ENZA) versus Olaparib Plus Abiraterone Acetate (OLAP+AAP) for first-line (1L) therapy in patients with metastatic Castration-Resistant Prostate Cancer (mCRPC): Unselected and Homologous Recombination Repair (HRR)-deficient populations