AIMS: Abiraterone treatment requires regular drug intake under fasting conditions due to pronounced food effect, which may impact patient adherence. The aim of this prospective study was to evaluate adherence to abiraterone treatment in patients with prostate cancer. To achieve this aim, an abiraterone population pharmacokinetic model was developed and patients' adherence has been estimated by comparison of measured levels of abiraterone with population model-based simulations. METHODS: A total of 1469 abiraterone plasma levels from 83 healthy volunteers collected in a bioequivalence study were analysed using a nonlinear mixed-effects model. Monte Carlo simulation was used to describe the theoretical distribution of abiraterone pharmacokinetic profiles at a dose of 1000 mg once daily. Adherence of 36 prostate cancer patients treated with abiraterone was then evaluated by comparing the real abiraterone concentration measured in each patient during follow-up visit with the theoretical distribution of profiles based on simulations. Patients whose abiraterone levels were ˂5th or ˃95th percentile of the distribution of simulated profiles were considered to be non-adherent. RESULTS: Based on this evaluation, 13 patients (36%) have been classified as non-adherent. We observed significant association (P = .0361) between richness of the breakfast and rate of non-adherence. Adherent patients reported significantly better overall condition in self-assessments (P = .0384). A trend towards a higher occurrence of adverse effects in non-adherent patients was observed. CONCLUSIONS: We developed an abiraterone population pharmacokinetic model and proposed an advanced approach to medical adherence evaluation. Due to the need for administration under fasting conditions, abiraterone therapy is associated with a relatively high rate of non-adherence.

Department of Analytical Chemistry Faculty of Science Charles University Prague Czech Republic

Department of Oncology 1st Faculty of Medicine Charles University and General University Hospital Prague Prague Czech Republic

Department of Oncology 1st Faculty of Medicine Charles University and Thomayer Hospital Prague Czech Republic

Department of Oncology 3rd Faculty of Medicine Charles University and Královské Vinohrady University Hospital Prague Czech Republic

Department of Oncology Krajská Nemocnice Liberec a s Liberec Czech Republic

Institute of Pharmacology 1st Faculty of Medicine Charles University and General University Hospital Prague Prague Czech Republic

Zentiva k s Prague Czech Republic

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Cassinello J, Dominguez‐Lubillo T, Gomez‐Barrera M, et al. Optimal treatment sequencing of abiraterone acetate plus prednisone and enzalutamide in patients with castration‐resistant metastatic prostate cancer: a systematic review and meta‐analysis. Cancer Treat Rev. 2021;93:102152. doi:10.1016/j.ctrv.2020.102152

Attard G, Reid AH, Yap TA, et al. Phase I clinical trial of a selective inhibitor of CYP17, abiraterone acetate, confirms that castration‐resistant prostate cancer commonly remains hormone driven. J Clin Oncol. 2008;26(28):4563‐4571. doi:10.1200/JCO.2007.15.9749

European Medicine Agency (EMA). Zytiga: Summary of Product Characteristics. https://www.ema.europa.eu/en/documents/product-information/zytiga-epar-product-information_en.pdf. Accessed: 2023, October 17.

Carton E, Noe G, Huillard O, et al. Relation between plasma trough concentration of abiraterone and prostate‐specific antigen response in metastatic castration‐resistant prostate cancer patients. Eur J Cancer. 2017;72:54‐61. doi:10.1016/j.ejca.2016.11.027

Baciarello G, Ozguroglu M, Mundle S, et al. Impact of abiraterone acetate plus prednisone in patients with castration‐sensitive prostate cancer and visceral metastases over four years of follow‐up: a post‐hoc exploratory analysis of the LATITUDE study. Eur J Cancer. 2022;162:56‐64. doi:10.1016/j.ejca.2021.11.026

Fizazi K, Scher HI, Molina A, et al. Abiraterone acetate for treatment of metastatic castration‐resistant prostate cancer: final overall survival analysis of the COU‐AA‐301 randomised, double‐blind, placebo‐controlled phase 3 study. Lancet Oncol. 2012;13(10):983‐992. doi:10.1016/S1470‐2045(12)70379‐0

van Nuland M, Groenland SL, Bergman AM, et al. Exposure–response analyses of abiraterone and its metabolites in real‐world patients with metastatic castration‐resistant prostate cancer. Prostate Cancer Prostatic Dis. 2020;23(2):244‐251. doi:10.1038/s41391‐019‐0179‐5

Stuyckens K, Saad F, Xu XS, et al. Population pharmacokinetic analysis of abiraterone in chemotherapy‐naïve and docetaxel‐treated patients with metastatic castration‐resistant prostate cancer. Clin Pharmacokinet. 53(12):1149‐1160.

Chien C, Smith M, De Porre P. Effect of food on abiraterone pharmacokinetics: a review. Int J Pharm. 2017;2(3):183‐193. doi:10.4155/ipk‐2016‐0026

Groenland SL, van Nuland M, Bergman AM, et al. Concomitant intake of abiraterone acetate and food to increase pharmacokinetic exposure: real life data from a therapeutic drug monitoring programme. Eur J Cancer. 2020;130:32‐38. doi:10.1016/j.ejca.2020.02.012

Chi KN, Spratlin J, Kollmannsberger C, et al. Food effects on abiraterone pharmacokinetics in healthy subjects and patients with metastatic castration‐resistant prostate cancer. J Clin Pharmacol. 2015;55(12):1406‐1414. doi:10.1002/jcph.564

Nikrynova Nguyen TMP, Strauch B, Petrak O, et al. Adherence and blood pressure control in patients with primary aldosteronism. Blood Press. 2022;31(1):58‐63. doi:10.1080/08037051.2022.2061416

Sima M, Vodicka M, Maresova V, Salek T, Cabala R, Slanar O. Adherence with perindopril therapy: a pilot study using therapeutic drug monitoring of perindoprilat and an evaluation of the clearance estimation. Int J Clin Pharmacol. 2017;39(5):1095‐1100. doi:10.1007/s11096‐017‐0522‐7

Boleslavska T, Rychecky O, Krov M, et al. Bioavailability enhancement and food effect elimination of abiraterone acetate by encapsulation in surfactant‐enriched oil marbles. AAPS J. 2020;22(6):122. doi:10.1208/s12248‐020‐00505‐5

Boleslavska T, Svetlik S, Zvatora P, et al. Preclinical evaluation of new formulation concepts for abiraterone acetate bioavailability enhancement based on the inhibition of pH‐induced precipitation. Eur J Pharm Biopharm. 2020;151:81‐90. doi:10.1016/j.ejpb.2020.04.005

European Medicines Agency (EMA), Committee for Medicinal Products for Human Use. ICH guideline M10 on bioanalytical method validation and study sample analysis. EMA/CHMP/ICH/172948/2019. https://www.ema.europa.eu/en/documents/scientific-guideline/ich-guideline-m10-bioanalytical-method-validation-step-5_en.pdf. Accessed October 13, 2023.

Suttmann H, Gleissner J, Huebner A, et al. Adherence measures for patients with metastatic castration‐resistant prostate cancer treated with abiraterone acetate plus prednisone: results of a prospective, cluster‐randomized trial. Cancers (Basel). 2020;12(9):2550. doi:10.3390/cancers12092550

Heiss BL, Geynisman DM, Martinez E, et al. Comparison of out‐of‐pocket costs and adherence between the two arms of the prospective, randomized abiraterone food effect trial. Support Care Cancer. 2022;30(3):2803‐2810. doi:10.1007/s00520‐021‐06670‐3

Fleshner NE, Alibhai SMH, Connelly KA, et al. Adherence to oral hormonal therapy in advanced prostate cancer: a scoping review. Ther Adv Med Oncol. 2023;15:17588359231152845. doi:10.1177/17588359231152845

Fallara G, Lissbrant IF, Styrke J, Montorsi F, Garmo H, Stattin P. Observational study on time on treatment with abiraterone and enzalutamide. PLoS ONE. 2020;15(12):e0244462. doi:10.1371/journal.pone.0244462

Lafeuille MH, Grittner AM, Lefebvre P, et al. Adherence patterns for abiraterone acetate and concomitant prednisone use in patients with prostate cancer. J Manag Care Spec Pharm. 2014;20(5):477‐484. doi:10.18553/jmcp.2014.20.5.477

Doshi JA, Jahnke J, Raman S, et al. Treatment utilization patterns of newly initiated oral anticancer agents in a national sample of Medicare beneficiaries. J Manag Care Spec Pharm. 2021;27(10):1457‐1468. doi:10.18553/jmcp.2021.27.10.1457

ten Ham RMT, van Nuland M, Vreman RA, et al. Cost‐effectiveness assessment of monitoring abiraterone levels in metastatic castration‐resistant prostate cancer patients. Value Health. 2021;24(1):121‐128. doi:10.1016/j.jval.2020.04.1838

Serritella AV, Strohbehn GW, Goldstein DA, Lichter AS, Ratain MJ. Interventional pharmacoeconomics: a novel mechanism for unlocking value. Clin Pharmacol Ther. 2020;108(3):487‐493. doi:10.1002/cpt.1853

Center for Drug Evaluation and Research. NDA: Clinical Pharmacology Review. Application number: 2023790Orig1s000. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202379orig1s000clinpharmr.pdf. Accessed: April 29, 2024.