Abiraterone Research Articles

Compatibility of hypokalaemia caused by low-dose prednisolone plus abiraterone acetate therapy for metastatic castration-resistant prostate cancer.

This study aimed to investigate the relationship between low-dose prednisolone (PSL) and the incidence of hypokalaemia at abiraterone acetate (abiraterone) plus PSL combination therapy targeting Japanese patients with metastatic castration-resistant prostate cancer (mCRPC). This retrospective observational study included 153 Japanese patients treated with abiraterone and PSL for mCRPC at Kariya Toyota General Hospital and Gifu General Medical Center between September 2014 and October 2022. The incidence of grade ≥ 2 hypokalaemia as well as serum potassium level variations and the continuous combination therapy duration were compared between the low-dose (5mg/day of PSL) and the standard-dose (10mg/day of PSL) groups. This study included 153 patient of which 95 were matched to establish the analysis population. The low-dose and the standard-dose groups consisted of 13 and 82 patients, respectively. No significant difference in the incidence of grade ≥ 2 hypokalaemia was observed between the two groups [15.4% (2/13 patients) in the low-dose group and 12.2% (10/82 patients) in the standard-dose group, P = 0.667]. The low-dose group exhibited a decrease in serum potassium levels from 4.63 on day - 7 - 0 to 4.16 mmol/L on day 84 ± 10 (n = 7, P = 0.066), and serum potassium levels from day - 7 - 0 to 84 ± 10 in the low-dose group appeared to be great in the standard-dose group (n = 37, P = 0.475). The Kaplan-Meier curves for continuity of abiraterone and PSL therapy were not significantly different between the low-dose group (n = 13) and standard-dose group (n = 82, P = 0.427). Combination therapy with abiraterone and 5mg/day of PSL in Japanese patients with mCRPC did not change the incidence of grade ≥ 2 hypokalaemia. However, although not significant, 5mg/day of PSL demonstrated a decreasing trend in serum potassium levels with a larger degree of change than that of 10mg/day of PSL. Therefore, the combination of abiraterone and 5mg/day PSL can be administered to Japanese patients with mCRPC. The patients must be monitored for hypokalaemia through measurement of serum potassium levels and observation of subjective symptoms such as muscle weakness, convulsion etc. In addition, the doctor or the pharmacist must explain these symptoms to the patient and instruct them to consult their medical staff immediately in the event of development of such symptoms.

Tumor regression after neoadjuvant hormonal therapy in high risk prostate cancer: pathological outcomes from a randomized phase II trial.

High-risk localized prostate cancer (HRLPC) commonly progresses to metastatic disease after local treatment. Neoadjuvant androgen deprivation therapy (nADT) before radical prostatectomy (RP) has recently been suggested to improve early oncological outcomes in HRLPC. We aimed to perform an exploratory analysis of the pathological outcomes from a prospective trial testing nADT before RP. Prospective, single-centered, phase II, randomized trial performed between October 2018 and July 2021. Random assignment (1:1) for nADT modalities: goserelin (10.8mg) plus abiraterone acetate (1000mg/d) plus prednisone (5mg/d), with or without apalutamide (240mg/d) for 12 weeks, followed by RP (within 30 days) and extended lymph node dissection. Baseline clinical and pathological variables were assessed in needle biopsies before nADT. Tumor regression was histologically evaluated in surgical specimens using the residual cancer burden index (RCB). Sixty-two patients reached the surgical phase. Good response (RCB ≤ 0.25cm³) was achieved in 14 patients (22.5%). Overall stage migration rate between baseline status (MRI before nADT) and final status (after surgery) was 27.4%. Late stage detection (high tumor burden, perineural invasion) and altered PTEN/ERG immunostatus showed significant association with poor response in univariate analysis. Higher baseline tumor burden was the only independent factor related to poor response in multivariate analysis. There are subgroups of patients, such as those with low baseline cancer burden and PTEN/ERG wild-type status, more likely to achieve good response with nADT. In the case of long term oncological benefit to be proven, nADT might be an additional therapeutic resource for these patients.

Androgen Receptor Signaling Inhibitor Withdrawal Syndrome After Castration-resistant Prostate Cancer.

Androgen-deprivation therapy is an extremely effective treatment for progressive prostate cancer. Previously, the first-line treatment for progressive prostate cancer was combined androgen blockade (CAB). If the disease progressed to castration-resistant prostate cancer, the administration of androgen receptor signaling inhibitors (ARSIs) was recommended. When elevated serum prostate-specific antigen (PSA) levels are seen during CAB treatment, it is important to suspect antiandrogen withdrawal syndrome (AWS), discontinue CAB, and monitor the changes in the serum PSA levels. If a reduction in the patient's PSA levels is subsequently observed, antiandrogens should be discontinued and the patient should be followed, but if their PSA level rises they should be transitioned to ARSI treatment. Recently, there have been reports of withdrawal syndrome (WS) after ARSI treatment. With the increased use of ARSIs, such as abiraterone acetate, enzalutamide, apalutamide, and dalorutamide, it is necessary to consider ARSI WS when a patient's serum PSA level increases during ARSI treatment. Unnecessary treatment can be avoided if the confirmation of ARSI WS is prioritized. Conversely, if it is not confirmed there is a risk that second-line treatment will be delayed. This is a review of recent studies of ARSI WS. It also discusses future prospects in this field.

P104 Concordance between response on prostate-specific membrane antigen positron emission tomography/computed tomography and biochemical response in patients with metastatic hormone-sensitive prostate cancer starting on androgen deprivation therapy plus apalutamide or abiraterone acetate

P104 Concordance between response on prostate-specific membrane antigen positron emission tomography/computed tomography and biochemical response in patients with metastatic hormone-sensitive prostate cancer starting on androgen deprivation therapy plus apalutamide or abiraterone acetate

P130 Cardiovascular (CV) events and Overall Survival (OS) in Patients (pts) treated with Abiraterone Acetate (AA) Vs ENzalutamide (ENZA) for chemotherapy-naïve metastatic Castration Resistant Prostate Cancer (mCRPC) in GERmany: AVENGER study

P130 Cardiovascular (CV) events and Overall Survival (OS) in Patients (pts) treated with Abiraterone Acetate (AA) Vs ENzalutamide (ENZA) for chemotherapy-naïve metastatic Castration Resistant Prostate Cancer (mCRPC) in GERmany: AVENGER study

P160 MEMORIAE: A multicenter prospective study evaluating cognitive functioning in patients (pts) with metastatic Castration ResIstant Prostate Cancer (mCRPC) treated with ABIraterone (ABI) or ENZAlutamide (ENZA)

P160 MEMORIAE: A multicenter prospective study evaluating cognitive functioning in patients (pts) with metastatic Castration ResIstant Prostate Cancer (mCRPC) treated with ABIraterone (ABI) or ENZAlutamide (ENZA)

Abiraterone and Galeterone, Powerful Tools Against Prostate Cancer: Present and Perspective

Due to the high prostate cancer incidence worldwide, the development of different methods of treatment continues to be a hot research topic. Since its first clinical application at the beginning of the 2010s, abiraterone in the form of prodrug abiraterone acetate continues to be the most used hormone derivative in the treatment of castration-resistant prostate cancer. This is the reason behind the publication of many scientific results regarding its synthesis, biological activity, metabolism, novel designed steroid derivatives based on its structure, etc. A similar steroid compound with a heterocycle in the C17 position, called galeterone, also designed to treat prostate cancer, continues to be in clinical studies, which provides further proof of the importance of these steroid derivatives. Besides prostate cancer treatment, abiraterone showed indications for possible clinical application in the treatment of breast, ovarian, lung, kidney, salivary gland, and adrenocortical cancer, congenital adrenal hyperplasia, Cushing’s syndrome, and COVID-19, while galeterone is investigated for its use against prostate, pancreatic, and breast cancer. Herein, we report a review comprising methods of synthesis, possible clinical applications, and mechanisms of action, as well as structures and bioactivities of derivatives of these two important steroids.

Predicting time to castration resistance with androgen-receptor signaling inhibitors in hormone-sensitive prostate cancer: data from ULTRA-Japan Consortium.

Androgen-receptor signaling inhibitors (ARSIs) become the new standard of care for metastatic hormone-sensitive prostate cancer (mHSPC). It is unknown whether time to castration resistance (TTCR), when using the first-line ARSIs, offers predictive value in mHSPC. We sought to assess the clinical outcomes for mHSPC patients treated with first-line ARSIs focusing on the TTCR. Data from the ULTRA-Japan study cohort from five academic institutes (496 mHSPC patients) were retrospectively analyzed. The median overall survival (OS) in the total cohort was 80months with a median follow-up of 18months. Of 496 patients, 332 (67%), 82 (16.5%), and 82 (16.5%) were treated with first-line abiraterone acetate + prednisone, enzalutamide, and apalutamide, respectively. During the follow-up, a total of 155 (31%) were diagnosed with mCRPC with a median TTCR of 10months. In those 155 patients, TTCR > 12months is an independent predictor of longer OS from the first-line ARSIs. Cox regression analysis of the TTCR from initiating first-line ARSI in 496 mHSPC patients revealed three variables as independent predictors of shorter TTCR, including Gleason's score (GS) ≥ 9, the extent of disease (EOD) ≥ 2, and the presence of liver metastasis. Our results indicate that mHSPC patients with those three features are likely to have primary resistance to first-line ARSIs (doublet therapy), thus requiring consideration of other options, such as the recent triplet approach.

Enzalutamide versus abiraterone acetate in the development of new-onset or worsening type 2 diabetes mellitus in patients with metastatic castration-resistant prostate cancer: EVADE study

PurposeTo determine new-onset or worsening T2DM risk in patients with metastatic castration-resistant prostate cancer (mCRPC) receiving abiraterone acetate (AA) vs. enzalutamide (ENZA) in England.MethodsRecords of patients on AA and/or ENZA (2015−2021) were analysed retrospectively from UK- or England-wide databases and data sets. The primary endpoint was new-onset or worsening T2DM, analysed using a Cox model.ResultsOf 1382 patients, 84 (6.1%) met the primary endpoint; 42 of 826 patients (5.1%) received ENZA and 42 of 556 patients (7.6%) received AA. Among patients without baseline T2DM (n = 1049), 50 developed new-onset T2DM: 24 (3.9%) on ENZA and 26 (5.9%) on AA. Among patients with baseline T2DM (n = 333), 34 (10.2%) had worsening T2DM: 18 (8.3%) on ENZA and 16 (13.8%) on AA. Patients on ENZA had longer median follow-up (445 vs. 408 days) and treatment duration (164 vs. 139 days) than those on AA, who were also more likely to have new-onset or worsening T2DM than those on ENZA (HR: 1.8; 95% CI: 1.4–2.7; P = 0.0101). The number needed to harm for an additional patient to experience new-onset or worsening T2DM when receiving AA instead of ENZA was 40 overall, 50 in patients without baseline T2DM, and 18 in patients with baseline T2DM.ConclusionPatients with mCRPC receiving AA were more likely to experience new-onset or worsening T2DM than those on ENZA, despite having a shorter treatment duration. Further research is required to substantiate these findings in earlier disease settings with longer treatment duration.

Development, Validation, and Greenness Assessment of Eco-Friendly Analytical Methods for the Determination of Abiraterone Acetate in Pure Form and Pharmaceutical Formulations

This study presents the development and validation of environmentally friendly analytical methods for quantifying Abiraterone Acetate (AA) in both its pure form and commercial pharmaceutical formulations. An optimized High-Performance Liquid Chromatography (HPLC) method was developed using an Agilent Extend C18 column (250 mm × 4.6 mm, 5 μm) at 25 °C. The mobile phase consisted of formic acid and ethanol in isocratic mode, with a flow rate of 1.0 mL min−1, and detection was performed at 253 nm. The spectrophotometric method involved a comprehensive evaluation of AA’s spectral properties in various solvents, with ultrapure water providing the most suitable spectra for analysis at 253 nm. Both methods were validated according to ICH guidelines, demonstrating selectivity, linearity, accuracy, precision, detection and quantification limits, and robustness, with correlation coefficients exceeding 0.999 across the 5–30 μg mL−1 concentration range. Comparative statistical analysis using Student’s t-test and Fisher’s F-test showed no significant differences between the two methods. The environmental impact of both methods was assessed using AGREE and GAPI software, confirming their sustainability. These validated methods offer reliable and eco-friendly approaches for the quantitative analysis of AA in tablet formulations, promoting safer and greener laboratory practices in pharmaceutical analysis.

Ruthenium complexes with abiraterone acetate as antiproliferative agents

This study is dedicated to the development of multimodal anticancer agents. We have obtained ruthenium complexes conjugated with the steroid-type antitumor drug abiraterone acetate in order to take advantage of the dual antitumor properties of both ruthenium and abiraterone. The compounds exhibit good antiproliferative activity against cancer cells, with selectivity over primary fibroblasts. Real-time cell analysis revealed that compound dichlorido(η66-p-cymene)(abiraterone acetate)ruthenium(II) had pronounced antiproliferation activity compared to abiraterone acetate. Flow cytometric studies on the mechanism of cell death have revealed that the most active compound induces apoptosis more effectively than abiraterone acetate. Our findings demonstrate the potential of this novel dual-action compound as promising candidates for further development as anticancer agents.

7906 Nanoencapsulated Curcumin-Piperine Complex: A Breakthrough In Targeting CYP17A1 For Castration Resistant Prostate Cancer Therapy

Abstract Disclosure: J. Yakubu: None. Nanoencapsulated Curcumin-Piperine Complex: A Breakthrough in Targeting CYP17A1 for Castration Resistant Prostate Cancer Therapy. Jibira Yakubu a,b,c, Oya Taritd, Evangelos Natsaridisd, Amit V. Pandey a,ba Translational Hormone Research Program, Department of Biomedical Research, Faculty of Medicine, b Paediatric Endocrinology, Diabetology and Metabolism, University Children’s Hospital, Inselspital, Bern, c Graduate School for Cellular and Biomedical Sciences, University of Bern, Bern, Switzerland. d Biointerfaces, Institute of Chemistry and Bioanalytics, University of Life Sciences FHNW, Muttenz, Switzerland. Abstract: Androgens play a pivotal role in prostate cell survival and are implicated in both early-stage and advanced, castration-resistant prostate cancer (CRPC). In CRPC patients on CYP17A1 inhibitors, the development of drug resistance and hypertensive crisis through the inhibition of CYP21A2 and or its substrate are a recognized challenge. Given its crucial role in androgen production, CYP17A1 has become a major target for cancer therapies. In this study, we employed a mini-evaporation technique to nanoencapsulate curcumin, exploring its impact on CYP17A1 activity in human adrenal NCI-H295R cells. We performed steroid profiling with LC-MS, as well as gene and protein expression studies. Initial results demonstrated that curcumin nanoparticles exhibited superior efficacy in reducing CYP17A1 activity compared to known drug Abiraterone acetate. Curcumin and piperine combined in nano-capsules greatly increased the inhibitory effects on CYP17A1 activity. Furthermore, ongoing studies include western blot investigation of the drug's interaction with the CYP17A1 protein and cell cycle effects. We confirmed the efficacy of our nano formulation by testing its impact on the growth of androgen-sensitive prostate cancer cell lines. Notably, nanoencapsulation improved curcumin's inhibitory effects on DHEA production via CYP17A1. Surprisingly, the curcumin-piperine nano-capsules enhanced these effects while having no effect on CYP21A2, offering a promising option for prostate cancer treatment. Our study reveals the promise of nanoencapsulated curcumin-piperine as a game-changing method for targeting CYP17A1 for improved prostate cancer therapy. The synergistic benefits observed in our study open new avenues for addressing the difficulties associated with androgen deprivation therapy. Funding: Cancer Research Switzerland grant number: KFS 5557-02-2022 Presentation: 6/3/2024

Are Nanostructured Lipid Carriers (NLC) better than Solid Lipid Nanoparticles (SLN) for delivering abiraterone acetate through the gastrointestinal tract?

Abiraterone acetate (AbA) is a progesterone derivative indicated for the treatment of metastatic prostate cancer. This BCS (Biopharmaceutics Classification System) Class IV molecule has an extremely poor oral bioavailability (<10 %), notably due to its very low water solubility and intestinal permeability. Among the few existing galenic strategies to improve AbA’s oral bioavailability, lipid nanoparticles such as Solid Lipid Nanoparticles (SLN) and Nanostructured Lipid Carriers (NLC) are relevant nanovectors. The objective of this study is to develop and compare SLN and NLC for oral delivery of abiraterone acetate. Both SLN and NLC are biocompatible, biodegradable and produced by high pressure homogenization (HPH), an ecological-friendly manufacturing process, organic solvent-free and easily scalable. The HPH process allowed the formation of AbA-loaded SLN and NLC with particle size lower than 160 nm and high encapsulation efficiencies. The addition of a liquid lipid significantly reduced the mean diameter of the nanoparticles, reflecting the greater benefit of the NLC formulation compared to SLN. Both SLN and NLC formulations offered an important protection of AbA in intestinal media, with a better stability for NLC. When encapsulated in SLN or NLC, the AbA is strongly retained by the nanoparticles, whatever the dissolution medium, which means that both formulas are able to protect and retain the drug in the intestinal tract, right up to its delivery to the enterocytes surface. High concentrations of nanoparticles were administered without cytotoxicity, especially for the NLC, which provides a real added value in terms of biocompatibility with Caco-2 cells. Finally, the nanoparticles were able to penetrate into enterocytes by the transcellular route, demonstrating an intense cellular internalization.

Docetaxel Versus Androgen-Receptor Signaling Inhibitors (ARSI) as Second-Line Therapy After Failure of First-Line Alternative ARSI for the Elderly ≥ 75 Years Old With Metastatic Castration-Resistant Prostate Cancer (mCRPC): A SPARTACUSS—Meet-URO 26 Real-World Study

BackgroundAndrogen receptor signalling inhibitors (ARSIs) abiraterone acetate (AA) enzalutamide (Enza), are currently the standard first-line (L1) treatments for metastatic castration-resistant prostate cancer (mCRPC), and docetaxel (D) is reserved as second-line (L2) after ARSI failure. Nonetheless, D use in men ≥ 75 years old is restricted owing to treatment toxicities and patient comorbidities, and a L2 alternative ARSI is frequently used. We aimed to evaluate real-life survival and toxicity outcomes of these elderly patients after failure of L1 ARSI treatment. Material and MethodsWe retrospectively evaluated efficacy and safety in a real-world international cohort of consecutive patients ≥ 75 years old when starting L1 ARSI for mCRPC according to the choice of L2 treatment (D versus alternative ARSI). ResultsOf the 122 identified patients, 57 (46.7%) had received L2 ARSI and 65 (53.3%) L2 D. No difference was found in the L1 overall survival (OS) for the ARSI and D groups (32.8 vs. 30.0 months, respectively; Hazard ratio [HR] = 1.22; 95% CI, 0.77-1.95; P = .40) or in the L2 OS (18.5 vs. 17.8 months, respectively; HR = 1.09; 95% CI, 0.69-1.74; P = .71). No difference was observed for rPFS from L2 (P = .12), although a trend was observed for a numerically improved rPFS on D. ConclusionWithin the limitations of a retrospective design and small population, our study suggests that D or ARSI after failure of L1 alternative ARSI are clinically comparable L2 options for elderly patients with mCRPC.

Prognostic model for second progression-free survival and overall survival in patients with high-risk metastatic hormone-sensitive prostate cancer treated with abiraterone acetate and androgen deprivation therapy.

To develop and validate a prognostic risk model for high-risk metastatic hormone-sensitive prostate cancer (mHSPC) patients treated with upfront abiraterone acetate (ABI). This retrospective multicenter study involved 233 high-risk mHSPC patients who received upfront ABI, developed by three academic centers. The model was externally validated with an independent cohort of 282 patients. To identify independent prognostic factors for second progression-free survival (PFS2) and develop the best-fitted model, Cox proportional hazards regression, followed by the Akaike information criterion, was used. Patients were categorized into three groups based on their risk scores. PFS2 and overall survival (OS) were evaluated according to the risk groups in the discovery and validation cohorts. The median age was 72 (range 51-89) years, with a median follow-up duration of 27 months. Independent factors linked to PFS2 included an Eastern Cooperative Oncology Group performance status ≥2, a primary Gleason score of 5, an extent of disease score of ≥3 or liver metastasis, and lactate dehydrogenase >220 U/L. Median PFS2 for favorable-, intermediate-, and poor-risk groups were not reached, 43 months, and 16 months, respectively. The median OS was 29 months in the poor-risk group, whereas it was not reached in the favorable- and intermediate-risk groups. The 2-year OS rates in the favorable-, intermediate- and poor-risk groups were 94.5%, 80.1%, and 60.3%, respectively. The validation cohort confirmed the risk model's relationship with PFS2 and OS. The median PFS2 and OS in the high-risk group were 21 months and 32 months, respectively. Our prognostic model, including five clinical factors, is useful for patient care and treatment selection in high-risk mHSPC patients treated with ADT plus ABI. The developed model could provide more accurate information, guide treatment decisions, or classify patients in future clinical trials.

Drug Interactions between Androgen Receptor Axis-Targeted Therapies and Antithrombotic Therapies in Prostate Cancer: Delphi Consensus.

Background/Objectives: Abiraterone acetate, apalutamide, darolutamide, and enzalutamide, which make up the androgen receptor axis-targeted therapies (ARATs) drug class, are commonly used in the management of prostate cancer. Many patients on ARATs also receive oral antithrombotic therapy (i.e., anticoagulants or antiplatelets). The concomitant use of ARATs and antithrombotic therapies creates the potential for clinically relevant drug-drug interactions, but the literature regarding the actual consequences of these interactions, and guidance for co-prescribing, is limited. We assembled a multidisciplinary panel of experts and provided them with clinical information derived from a comprehensive literature review regarding the drug-drug interactions between ARATs and antithrombotic therapies. Methods: A three-stage modified electronic Delphi process was used to gather and consolidate opinions from the panel. Each stage consisted of up to three rounds of voting to achieve consensus on which ARAT/antithrombotic therapy drug pairs warrant attention, the possible clinical consequences of drug-drug interactions, and suggested actions for management. Results: The panel achieved consensus to avoid 11 ARAT/antithrombotic therapy drug pairs and modify therapy for eight pairs. Assessments relied heavily on pharmacokinetic data and extrapolation from drug-drug interaction studies of similarly metabolized drugs. Conclusions: This e-Delphi process highlights the need for further research into the clinical impact of ARAT/antithrombotic drug interactions. Nonetheless, the suggested actions aim to provide clinicians with a practical framework for therapeutic decision making.

Connecting Gene Variation to Treatment Outcomes in Metastatic Castration-Resistant Prostate Adenocarcinoma: Insights into Second-Generation Androgen Receptor Axis-Targeted Therapies.

Prostate cancer (PC) is one of the most commonly diagnosed tumours among men. Second-generation androgen receptor axis-targeted (ARAT) agents, namely abiraterone acetate (AbA) and enzalutamide (ENZ), are currently used in the management of metastatic castration-resistant PC (mCRPC). However, the treatment is challenging due to the lack of prognostic biomarkers. Meanwhile, single-nucleotide polymorphisms (SNPs) have emerged as potential prognostic indicators of mCRPC. Thus, this study evaluated the impact of relevant SNPs on the treatment outcomes of 123 mCRPC patients enrolled in a hospital-based cohort study. The CYP17A1 rs2486758 C allele was associated with a 50% reduction in the risk of developing castration resistance (hazard ratio (HR) = 0.55; p = 0.003). Among patients without metastasis at tumour diagnosis and under AbA, a marginal association between YBX1 rs10493112 and progression-free survival was detected (log-rank test, p = 0.056). In the same subgroup, significant associations of HSD3B1 rs1047303 (CC/CA vs. AA; HR = 3.41; p = 0.025), YBX1 rs12030724 (AT vs. AA; HR = 3.54; p = 0.039) and YBX1 rs10493112 (log-rank test, p = 0.041; CC vs. AA/AC; HR = 3.22; p = 0.053) with overall survival were also observed, which were confirmed by multivariate Cox analyses. Although validation with larger cohorts is required, these findings suggest that SNPs could enhance the prognosis assessment of mCRPC patients, leading to a more personalised treatment.

Body composition in recurrent prostate cancer and the role of steroidogenic genotype.

Hormone therapy (HT) to treat prostate cancer is reported to cause adverse changes in body composition. Clinically, interpatient body composition changes are heterogeneous, but the biologic and clinical determinants of body composition toxicity are unknown. Herein, we test the hypothesis that inherited polymorphisms in steroidogenic genes are associated with differential change in body composition after HT. Men with biochemically recurrent prostate cancer (BCR) who received 8 months of LHRH analog (LHRHa) +/- abiraterone acetate (AAP) were eligible if they had: 1) CT imaging of L3 prior to and after treatment, and 2) nucleated cells collected. Cardiometabolic co-morbidities were retrospectively extracted. Body composition was measured using an AI-based segmentation tool. Germline DNA whole exome or genome sequencing was performed. In 162 men treated with 8 months of HT, median skeletal muscle mass (SMMi) loss was 6.6% and subcutaneous adipose gain was 12.3%. Men with type 2 diabetes had higher loss of SMMi after treatment (-11.1% vs. -6.3%, p = 0.003). For the 150 men with germline NGS, SRD5A2 rs523349 genotype was associated with differential loss in skeletal muscle density after HT, (-1.3% vs. -7.1%, p=0.04). In addition, HSD3B1 rs104703 genotype was associated with decreased baseline visceral adipose tissue (63.0 cm2/m2 vs. 77.9, p=0.05). In men with BCR, HT induced notable loss of skeletal muscle and increased subcutaneous adipose tissue. An inherited polymorphism in SRD5A2 and T2DM were associated with differential skeletal muscle toxicity. These findings suggest that inherited polymorphisms may contribute to the body composition toxicity observed with HT.

1650P Fuzuloparib plus abiraterone acetate and prednisone (AA-P) in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC): A phase I study

1650P Fuzuloparib plus abiraterone acetate and prednisone (AA-P) in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC): A phase I study

1662TiP HARMONY: A phase II study of niraparib (N)/abiraterone acetate (AA) plus prednisone (P) for Hispanic/Latino (HL) and non-Hispanic Black (NHB) patients (pts) with metastatic hormone sensitive prostate cancer (mHSPC) and deleterious homologous recombination repair alterations (HRRa)

1662TiP HARMONY: A phase II study of niraparib (N)/abiraterone acetate (AA) plus prednisone (P) for Hispanic/Latino (HL) and non-Hispanic Black (NHB) patients (pts) with metastatic hormone sensitive prostate cancer (mHSPC) and deleterious homologous recombination repair alterations (HRRa)