Inherited Variants in SULT1E1 and Response to Abiraterone Acetate by Men with Metastatic Castration Refractory Prostate Cancer

Agarwal, Neeraj; Alex, Anitha; Farnham, James M.; Patel, Shiven B.; Gill, David; Buckley, Tyler Howard; Stephenson, Robert A.; Cannon-Albright, Lisa

doi:10.1016/j.juro.2016.04.079

Cited by 12 publications

(5 citation statements)

References 22 publications

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“…Other biological analytical approaches, such as those based on tumor immunohistochemistry, could bring more firmly established answers on that point. In complement to the herein-considered SNPs, mention must be given to the study by Agarwal et al [ 23 ], having shown a link between SNPs in the SULT 1 E 1 gene and time to treatment failure for prostate cancer patients under AA.…”

Section: Discussionmentioning

confidence: 99%

Abigene, a Prospective, Multicentric Study of Abiraterone Acetate Pharmacogenetics in Metastatic Castration-Resistant Prostate Cancer

et al. 2023

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Abiraterone acetate (AA) is the first-in-class of drugs belonging to the second-generation of agents inhibiting androgen neosynthesis in advanced prostate cancer. A cumulative experience attests that germinal gene polymorphisms may play a role in the prediction of anticancer agent pharmacodynamics variability. In the present prospective, multicentric study, gene polymorphisms of CYP17A1 (AA direct target) and the androgen transporter genes SLCO2B1 and SLCO1B3 (potential modulators of AA activity) were confronted with AA pharmacodynamics (treatment response and toxicity) in a group of 137 advanced prostate cancer patients treated in the first line by AA. The median follow-up was 56.3 months (95% CI [52.5–61]). From multivariate analysis, rs2486758 C/C (CYP17A1) and PSA (≥10 ng/mL) were associated with a shorter 3-year biological PFS (HR = 4.05, IC95% [1.46–11.22]; p = 0.007 and HR = 2.08, IC95% [1.31–3.30]; p = 0.002, respectively). From a multivariate analysis, the rs743572 (CYP17A1) and performance status were independently associated with significant toxicity (OR = 3.78 (IC95% [1.42–9.75]; p = 0.006 and OR = 4.54; IC95% [1.46–13.61]; p = 0.007, respectively). Host genome characteristics may help to predict AA treatment efficacy and identify patients at risk for toxicity.

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Section: Discussionmentioning

confidence: 99%

Abigene, a Prospective, Multicentric Study of Abiraterone Acetate Pharmacogenetics in Metastatic Castration-Resistant Prostate Cancer

et al. 2023

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“…It is possible that diversity in gene expression and mutation among hormone-metabolizing enzyme genes, oncogenes, and suppressor genes and the difference in copy number variation and microsatellite instability could explain at least some of the racial disparities observed in survival. 27,28 Liu et al 29 found that Black and white patients had more prominent drug metabolism, cytotoxic therapy resistance, and endocrine therapy resistance than Asians. Prizment et al 30 demonstrated that the critical androgen-regulating gene HSD3B1 mutated differently among different races.…”

Section: Discussionmentioning

confidence: 99%

Impact of Asian Race on Prognosis in De Novo Metastatic Prostate Cancer

Michael

et al. 2023

Journal of the National Comprehensive Cancer Network

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Background: Little is known about the impact of Asian race on the long-term survival outcomes of males with de novo metastatic prostate cancer (PCa). Understanding racial disparities in survival is critical for accurate prognostic risk stratification and for informing the design of multiregional clinical trials. Methods: This multiple-cohort study included individual patient-level data for males with de novo metastatic PCa from the following 3 cohorts: LATITUDE clinical trial data (n=1,199), the SEER program (n=15,476), and the National Cancer Database (NCDB; n=10,366). Primary outcomes were overall survival (OS) in LATITUDE and NCDB and OS and cancer-specific survival in SEER. Results: Across all 3 cohorts, Asian patients diagnosed with de novo metastatic PCa had better survival than white patients. In LATITUDE, median OS was significantly longer in Asian versus white patients in the androgen deprivation therapy (ADT) + abiraterone + prednisone group (not reached vs 43.8 months; hazard ratio [HR], 0.45; 95% CI, 0.28–0.73; P=.001) as well as in the ADT + placebo group (57.6 vs 32.7 months; HR, 0.51; 95% CI, 0.33–0.78; P=.002). In SEER, among all patients diagnosed with de novo metastatic PCa, median OS was significantly longer in Asian versus white males (49 vs 39 months; HR, 0.76; 95% CI, 0.68–0.84; P<.001). Among those who received chemotherapy, Asian patients again had longer OS (52 vs 42 months; HR, 0.71; 95% CI, 0.52–0.96; P=.025). Using data on cancer-specific survival in SEER resulted in similar conclusions. In NCDB, Asian patients also had longer OS than white patients in aggregate and in subgroups of males treated with ADT or chemotherapy (aggregate: 38 vs 26 months; HR, 0.72; 95% CI, 0.62–0.83; P<.001; ADT subgroup: 41 vs 26 months; HR, 0.71; 95% CI, 0.60–0.84; P<.001; chemotherapy subgroup: 34 vs 25 months; HR, 0.67; 95% CI, 0.57–0.78; P<.001). Conclusions: Asian males have better OS and cancer-specific survival than white males with metastatic PCa across different treatment regimens. This should be considered when assessing prognosis and in designing multinational clinical trials.

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“…These may have contributed to the observed effects but were not evaluated in our study, which investigated germline factors for determining response to treatment. Furthermore, in a small study, germline variation in other signaling pathways such as the SULT1E1 variants described by Agarwal et al [ 36 ] has been shown to have effects on duration of response and warrant validation. The aforementioned factors will need to be evaluated in concert with our findings to gain a better understanding of the different factors affecting response to treatment.…”

Section: Discussionmentioning

confidence: 99%

Common Genetic Variation in CYP17A1 and Response to Abiraterone Acetate in Patients with Metastatic Castration-Resistant Prostate Cancer

Binder

Zhang

Hillman

et al. 2016

IJMS

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Treatment with abiraterone acetate and prednisone (AA/P) prolongs survival in metastatic castration-resistant prostate cancer (mCRPC) patients. We evaluated the genetic variation in CYP17A1 as predictive of response to AA/P. A prospective collection of germline DNA prior to AA/P initiation and follow-up of a mCRPC cohort was performed. Five common single-nucleotide polymorphisms (SNPs) in CYP17A1 identified using a haplotype-based tagging algorithm were genotyped. Clinical outcomes included biochemical response and time to biochemical progression on AA/P. Logistic regression was used to assess the association between tag SNPs and biochemical response. Proportional hazards regression was used to assess the association between tag SNPs and time to biochemical progression. Odds or hazard ratio per minor allele were estimated and p-values below 0.05 were considered statistically significant. Germline DNA was successfully genotyped for four tag SNPs in 87 patients. The median age was 73 years (54–90); the median prostate-specific antigen was 66 ng/dL (0.1–99.9). A single SNP, rs2486758, was associated with lower odds of experiencing a biochemical response (Odds ratio 0.22, 95% confidence interval 0.07–0.63, p = 0.005) and a shorter time to biochemical progression (Hazard ratio 2.23, 95% confidence interval 1.39–3.56, p < 0.001). This tag SNP located in the promoter region of CYP17A1 will need further validation as a predictive biomarker for AA/P therapy.

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Inherited Variants in SULT1E1 and Response to Abiraterone Acetate by Men with Metastatic Castration Refractory Prostate Cancer

Abstract: Single nucleotide polymorphisms in SULT1E1 were significantly associated with time to treatment failure in men on abiraterone acetate therapy. The single nucleotide polymorphisms may serve as predictive markers for treatment with abiraterone acetate.

Cited by 12 publications

References 22 publications

Abigene, a Prospective, Multicentric Study of Abiraterone Acetate Pharmacogenetics in Metastatic Castration-Resistant Prostate Cancer

Abigene, a Prospective, Multicentric Study of Abiraterone Acetate Pharmacogenetics in Metastatic Castration-Resistant Prostate Cancer

Impact of Asian Race on Prognosis in De Novo Metastatic Prostate Cancer

Common Genetic Variation in CYP17A1 and Response to Abiraterone Acetate in Patients with Metastatic Castration-Resistant Prostate Cancer

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