Dataset Information

Association Between CYP17A1, CYB5A Polymorphisms and Efficacy of Abiraterone Acetate/Prednisone Treatment in Castration-Resistant Prostate Cancer Patients.

ABSTRACT:

Purpose

The purpose of this study was to investigate the association between single nucleotide polymorphisms (SNPs) of CYP17A1, CYB5A and the efficacy of abiraterone acetate treatment in patients with castration-resistant prostate cancer (CRPC).

Patients and methods

Data were collected from 58 CRPC patients who had been treated with abiraterone acetate/prednisone (AA/P). The SNPs rs743572 and rs10883783 on CYP17A1 and SNPs rs1790834 and rs1790858 on CYB5A were assayed, and their relationship with prostate-specific antigen (PSA) response in patients after AA/P treatment, overall survival (OS) and progression-free survival (PFS) were analyzed by logistic regression, Cox regression, Kaplan-Meier and Log rank analyses.

Results

The SNP rs1790834 on CYB5A showed significant association with PSA response in CRPC patients treated with AA/P (P < 0.05), but rs743572, rs10883783 and rs1790858 did not. The rs1790834 variant significantly decreased both PFS and OS (P < 0.05).

Conclusion

The CYB5A rs790834 genotype is a novel SNP related to CRPC and may be used as a biomarker for CRPC treatment.

SUBMITTER: Wu X

PROVIDER: S-EPMC7280245 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Association Between CYP17A1, CYB5A Polymorphisms and Efficacy of Abiraterone Acetate/Prednisone Treatment in Castration-Resistant Prostate Cancer Patients.

Wu Xiang X Xu Qing-Jiang QJ Chen Ping-Zhou PZ Yu Chen-Bo CB Ye Lie-Fu LF Li Tao T

Pharmacogenomics and personalized medicine 20200604

<h4>Purpose</h4>The purpose of this study was to investigate the association between single nucleotide polymorphisms (SNPs) of CYP17A1, CYB5A and the efficacy of abiraterone acetate treatment in patients with castration-resistant prostate cancer (CRPC).<h4>Patients and methods</h4>Data were collected from 58 CRPC patients who had been treated with abiraterone acetate/prednisone (AA/P). The SNPs rs743572 and rs10883783 on CYP17A1 and SNPs rs1790834 and rs1790858 on CYB5A were assayed, and their r ...[more]

PMID: 32581567

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Project description:PurposeMetastatic castration-resistant prostate cancer (mCRPC) remains a lethal disease with current standard-of-care therapies. Homologous recombination repair (HRR) gene alterations, including BRCA1/2 alterations, can sensitize cancer cells to poly (ADP-ribose) polymerase inhibition, which may improve outcomes in treatment-naïve mCRPC when combined with androgen receptor signaling inhibition.MethodsMAGNITUDE (ClinicalTrials.gov identifier: NCT03748641) is a phase III, randomized, double-blinded study that evaluates niraparib and abiraterone acetate plus prednisone (niraparib + AAP) in patients with (HRR+, n = 423) or without (HRR-, n = 247) HRR-associated gene alterations, as prospectively determined by tissue/plasma-based assays. Patients were assigned 1:1 to receive niraparib + AAP or placebo + AAP. The primary end point, radiographic progression-free survival (rPFS) assessed by central review, was evaluated first in the BRCA1/2 subgroup and then in the full HRR+ cohort, with secondary end points analyzed for the full HRR+ cohort if rPFS was statistically significant. A futility analysis was preplanned in the HRR- cohort.ResultsMedian rPFS in the BRCA1/2 subgroup was significantly longer in the niraparib + AAP group compared with the placebo + AAP group (16.6 v 10.9 months; hazard ratio [HR], 0.53; 95% CI, 0.36 to 0.79; P = .001). In the overall HRR+ cohort, rPFS was significantly longer in the niraparib + AAP group compared with the placebo + AAP group (16.5 v 13.7 months; HR, 0.73; 95% CI, 0.56 to 0.96; P = .022). These findings were supported by improvement in the secondary end points of time to symptomatic progression and time to initiation of cytotoxic chemotherapy. In the HRR- cohort, futility was declared per the prespecified criteria. Treatment with niraparib + AAP was tolerable, with anemia and hypertension as the most reported grade ≥ 3 adverse events.ConclusionCombination treatment with niraparib + AAP significantly lengthened rPFS in patients with HRR+ mCRPC compared with standard-of-care AAP.[Media: see text].

Project description:IntroductionProstate cancer (PC) is the second leading cause of cancer death among US men and accounts for considerable healthcare expenditures. We evaluated economic outcomes in men with chemotherapy-naïve metastatic castration-resistant PC (mCRPC) treated with enzalutamide or abiraterone acetate plus prednisone (abiraterone).MethodsWe performed a retrospective analysis on 3174 men (18 years or older) utilizing the Veterans Health Administration (VHA) database from 1 April 2014 to 31 March 2018. Men with mCRPC were included if they had at least one pharmacy claim for enzalutamide or abiraterone (first claim date = index date) following surgical or medical castration, had no chemotherapy treatment within 12 months prior to the index date, and had continuous VHA enrollment for at least 12 months pre- and post-index date. Men were followed until death, disenrollment, or end of study and were 1:1 propensity score matched (PSM). All-cause and PC-related resource use and costs per patient per month (PPPM) in the 12 months post index were compared between matched cohorts.ResultsWe identified 1229 men with mCRPC prescribed enzalutamide and 1945 prescribed abiraterone with mean ages of 74 and 73 years, respectively. After PSM, each cohort had 1160 patients. The enzalutamide cohort had fewer all-cause (2.51 vs 2.86; p < 0.0001) and PC-related outpatient visits (0.86 vs 1.03; p < 0.0001), with corresponding lower all-cause ($2588 vs $3115; p < 0.0001) and PC-related ($1356 vs $1775; p < 0.0001) PPPM outpatient costs compared with the abiraterone cohort. All-cause total costs (medical and pharmacy) PPPM ($8085 vs $9092; p = 0.0002) and PC-related total costs PPPM ($6321 vs $7280; p < 0.0001) were significantly lower in the enzalutamide cohort compared with the abiraterone cohort.ConclusionsEnzalutamide-treated men with chemotherapy-naïve mCRPC had significantly lower resource utilization and healthcare costs compared with abiraterone-treated men.

Dataset Information

Association Between CYP17A1, CYB5A Polymorphisms and Efficacy of Abiraterone Acetate/Prednisone Treatment in Castration-Resistant Prostate Cancer Patients.

Purpose

Patients and methods

Results

Conclusion

Publications

Association Between CYP17A1, CYB5A Polymorphisms and Efficacy of Abiraterone Acetate/Prednisone Treatment in Castration-Resistant Prostate Cancer Patients.

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