Second-generation androgen receptor inhibitors in therapy of non-metastatic castration resistant prostate cancer: role of safety profile and effect on quality of life
pdf (Русский)

Keywords

non-metastatic castration resistant prostate cancer
second-generation androgen receptor inhibitors
Enzalutamide
Apalutamide
Darolutamide

How to Cite

Ushkalova, E., Zyryanov, S., & Gopienko, I. (2022). Second-generation androgen receptor inhibitors in therapy of non-metastatic castration resistant prostate cancer: role of safety profile and effect on quality of life. Voprosy Onkologii, 67(2), 217–226. https://doi.org/10.37469/0507-3758-2021-67-2-217-226

Abstract

The article discusses the role of second-generation androgen receptor inhibitors (ARi) in therapy of non-metastatic castration resistant prostate cancer (nmCRPC). The phase 3 trials PROSPER (enzalutamide), SPARTAN (apalutamide) and ARAMIS (darolutamide) showed that these medicines if used in combination with androgen deprivation therapy (ADT) make possible to significantly improve, as compared with placebo, metastasis-free survival and overall survival of patients with nmCRPC. An important role in choosing a certain medicine of the group is played by its safety profile, including its drug-drug interaction potential and effect on patient’s quality of life. In this respect, darolutamide has a number of advantages over apalutamide or enzlutamide. The frequency of CNS (cognitive, psychiatric, convulsive) and other adverse drug reactions that significantly worsen the patients’ quality of life (falls, fractures, hypertension, etc.) in therapy with darolutamide does not differ from that with placebo. Moreover, this medicine retains its antagonistic effects to all clinically significant androgen receptor mutations that develop resistance to enzalutamide and apalutamide.

https://doi.org/10.37469/0507-3758-2021-67-2-217-226
pdf (Русский)

References

Bray F., Ferlay J., Soerjomataram I. et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68(6):394–424. doi: 10.3322/caac.21492.

Злокачественные новообразования в России в 2018 году (заболеваемость и смертность) / А.Д. Каприн, В.В. Старинский, Г.В. Петрова. - Москва: МНИОИ им. П.А. Герцена филиал ФГБУ «ФМИЦ им. П.А. Герцена» Минздрава России, 2019:250. [Malignancies in Russia in 2018 (morbidity and mortality). Ed. A.D. Kaprin, V.V. Starinskii, G.V. Petrova. - Moscow, Moskovskii nauchno-issledovatel’skii onkologicheskii institut imeni P.A. Gertsena, 2019:250 (In Russ.)].

Boyle H.J., Alibhai S., Decoster L. et al. Updated recommendations of the International Society of Geriatric Oncology on prostate cancer management in older patients. Eur J Cancer. 2019 Jul;116:116-136. doi: 10.1016/j.ejca.2019.04.031.

Fizazi K., Smith M.R., Tombal B. Clinical Development of Darolutamide: A Novel Androgen Receptor Antagonist for the Treatment of Prostate Cancer. Clin Genitourin Cancer. 2018 Oct;16(5):332-340. doi: 10.1016/j.clgc.2018.07.017.

Ritch C, Cookson M. Recent trends in the management of advanced prostate cancer. F1000Res. 2018 Sep 21;7:F1000 Faculty Rev-1513. doi: 10.12688/f1000research.15382.1.

Tombal B., Miller K., Boccon-Gibod L. et al. Additional analysis of the secondary end point of biochemical recurrence rate in a phase 3 trial (CS21) comparing degarelix 80 mg versus leuprolide in prostate cancer patients segmented by baseline characteristics. Eur Urol. 2010;57 (5):836–42.

Lowrance W.T., Murad M.H., Oh W.K. et al. Castration-resistant prostate cancer: AUA guideline amendment 2018. J Urol. 2018;200(6):1264–1272. doi:10.1016/j.juro.2018.07.090.2.

Алексеев Б.Я., Нюшко К.М., Козлова П.С. и др. Современные возможности терапии больных неметастатическим кастрационно-рефрактерным раком предстательной железы. Онкоурология 2020; 16 (3): 190-197. [Alekseev B.Y., Nushko K.M., Kozlova P.S. et al. Current opportunities of therapy for patients with non-metastatic castration-resistant prostate cancer. Cancer Urology. 2020;16(3):190-197. (In Russ.)].

Sumanasuriya S., De Bono J. Treatment of Advanced Prostate Cancer-A Review of Current Therapies and Future Promise. Cold Spring Harb Perspect Med. 2018 Jun 1;8(6):a030635. doi: 10.1101/cshperspect.a030635.

Liede A.J. Arellano, G. Hechmati, B. Bennett, Wong S. International prevalence of nonmetastatic (M0) castration-resistant prostate cancer (CRPC). J Clin Oncol. 2013;31(suppl 15):e16052.

Mansinho A., Macedo D., Fernandes I., Costa L. Castration-Resistant Prostate Cancer: Mechanisms, Targets and Treatment. Adv Exp Med Biol. 2018;1096:117-133. doi: 10.1007/978-3-319-99286-0_7.

Kirby M., Hirst C., Crawford E.D. Characterising the castration-resistant prostate cancer population: a systematic review. Int J Clin Pract. 2011 Nov;65(11):1180-92. doi: 10.1111/j.1742-1241.2011.02799.x.

Hirst C.J., Cabrera C., Kirby M. Epidemiology of castration resistant prostate cancer: a longitudinal analysis using a UK primary care database. Cancer Epidemiol. 2012 Dec;36(6):e349-53. doi: 10.1016/j.canep.2012.07.012.

Smith M.R., Kabbinavar F., Saad F. et al. Natural history of rising serum prostate-specific antigen in men with castrate nonmetastatic prostate cancer. J Clin Oncol. 2005;23(13):2918–25. 10.1200/JCO.2005.01.529.

Alpajaro S.I.R., Harris J.A.K., Evans C.P. Non-metastatic castration resistant prostate cancer: a review of current and emerging medical therapies. Prostate Cancer Prostatic Dis. 2019 Mar;22(1):16-23. doi: 10.1038/s41391-018-0078-1.

Donovan K.A., Walker L.M., Wassersug R.J. et al. Psychological effects of androgen deprivation therapy on men with prostate cancer and their partners. Cancer. 2015;121(24):4286-4299. doi:10.1002/cncr.29672.

Sartor O., Flood E., Beusterien K. et al. Health-related quality of life in advanced prostate cancer and its treatments: biochemical failure and metastatic disease populations. Clin Genitourin Cancer. 2015 Apr;13(2):101-12. doi: 10.1016/j.clgc.2014.08.001.

Northouse L.L., Mood D.W., Montie J.E. et al. Living with prostate cancer: patients' and spouses' psychosocial status and quality of life. J Clin Oncol. 2007 Sep 20;25(27):4171-7. doi: 10.1200/JCO.2006.09.6503.

Shevach J., Weiner A., Morgans A.K. Quality of Life-Focused Decision-Making for Prostate Cancer. Curr Urol Rep. 2019 Aug 29;20(10):57. doi: 10.1007/s11934-019-0924-2.

Beijer H.J., de Blaey C.J. Hospitalisations caused by adverse drug reactions (ADR): a meta-analysis of observational studies. Pharm World Sci. 2002 Apr;24(2):46-54. doi: 10.1023/a:1015570104121.

Alhawassi T.M., Krass I., Bajorek B.V., Pont L.G. A systematic review of the prevalence and risk factors for adverse drug reactions in the elderly in the acute care setting. Clin Interv Aging. 2014 Dec 1;9:2079-86. doi: 10.2147/CIA.S71178.

Putilina M.V. [Comorbidity in elderly patients]. Zh Nevrol Psikhiatr Im S S Korsakova. 2016;116(5):106-111. Russian. doi: 10.17116/jnevro201611651106-111.

Carneiro J.A., Cardoso R.R., Durães M.S. et al. Frailty in the elderly: prevalence and associated factors. Rev Bras Enferm. 2017 Jul-Aug;70(4):747-752. doi: 10.1590/0034-7167-2016-0633.

Srinivas S., Mohamed A.F., Appukkuttan S. et al. Patient and caregiver benefit-risk preferences for nonmetastatic castration-resistant prostate cancer treatment. Cancer Med. 2020 Jul 29;9(18):6586–96. doi: 10.1002/cam4.3321.

Srinivas S., Mohamed A.F., Appukkuttan S. et al. Physician preferences for non-metastatic castration-resistant prostate cancer treatment. BMC Urol. 2020 Jun 22;20(1):73. doi: 10.1186/s12894-020-00631-4.

Wong R.L., Morgans A.K. Integration of Patient Reported Outcomes in Drug Development in Genitourinary Cancers. Curr Oncol Rep. 2020 Feb 8;22(3):21. doi: 10.1007/s11912-020-0890-3.

Scher H.I., Solo K., Valant J. et al. Prevalence of Prostate Cancer Clinical States and Mortality in the United States: Estimates Using a Dynamic Progression Model. PLoS One. 2015 Oct 13;10(10):e0139440. doi: 10.1371/journal.pone.0139440.

Lowrance W.T., Murad M.H., Oh W.K. et al. Castration-Resistant Prostate Cancer: AUA Guideline Amendment 2018. J Urol. 2018 Dec;200(6):1264-1272. doi: 10.1016/j.juro.2018.07.090.

Saad F., Mehra M., Small E. et al. Population-based study of the association of prostate -specific antigen doubling time (PSADT) with metastasis-free survival (MFS) and overall survival (OS) in nonmetastatic castration-resistant prostate cancer (NMCRPC) patients (PTS).J Urol 2018; 199 (4S) Supplement:e229.

Mostaghel E.A., Montgomery B., Nelson P.S. Castration-resistant prostate cancer: targeting androgen metabolic pathways in recurrent disease. Urol Oncol. 2009 May-Jun;27(3):251-7. doi: 10.1016/j.urolonc.2009.03.016.

IIsaacsson Velho P., Carducci M.A. Investigational therapies targeting the androgen signaling axis and the androgen receptor and in prostate cancer - recent developments and future directions. Expert Opin Investig Drugs. 2018 Oct;27(10):811-822. doi: 10.1080/13543784.2018.1513490.

Rice M.A., Malhotra S.V., Stoyanova T. Second-Generation Antiandrogens: From Discovery to Standard of Care in Castration Resistant Prostate Cancer. Front Oncol. 2019 Aug 28;9:801. doi: 10.3389/fonc.2019.00801.

Smith M.R., Saad F., Chowdhury S. et al. Apalutamide Treatment and Metastasis-free Survival in Prostate Cancer. N Engl J Med. 2018;378(15):1408–18. 10.1056/NEJMoa1715546.

Hussain M., Fizazi K., Saad F. et al. PROSPER: A phase 3, randomized, double-blind, placebo (PBO)-controlled study of enzalutamide (ENZA) in men with nonmetastatic castration-resistant prostate cancer (M0 CRPC). J Clin Oncol. 2018;36(6_suppl):3 10.1200/JCO.2018.36.6_suppl.3.

Fizazi K., Shore N., Tammela T.L. et al. Darolutamide in nonmetastatic, castration-resistant prostate cancer. N Engl J Med. 2019;380(13):1235–1246. doi:10.1056/NEJMoa1815671.

Small E.J., Saad F., Chowdhury S. et al. Apalutamide and overall survival in non‐metastatic castration‐resistant prostate cancer. Ann Oncol 2019;30(11):1813–1820. doi: 10.1093/annonc/mdz397.

Sternberg C.N., Fizazi K., Saad F. et al. Enzalutamide and survival in nonmetastatic, castration‐resistant prostate cancer. N Engl Med. 2020;382(23):2197–2206. doi: 10.1056/NEJMoa2003892.

Fizazi K., Shore N., Tammela T.L. et al. ARAMIS Investigators. Nonmetastatic, Castration-Resistant Prostate Cancer and Survival with Darolutamide. N Engl J Med. 2020 Sep 10;383(11):1040-1049. doi: 10.1056/NEJMoa2001342.

Fizazi K., Albiges L., Loriot Y., Massard C. ODM-201: A new-generation androgen receptor inhibitor in castration-resistant prostate cancer. Expert Rev. Anticancer Ther. 2015;15:1007–1017. doi: 10.1586/14737140.2015.1081566.

Moilanen A-M., Riikonen R., Oksala R. et al. Discovery of ODM-201, a new-generation androgen receptor inhibitor targeting resistance mechanisms to androgen signaling-directed prostate cancer therapies. Sci Rep. (2015) 5:12007 10.1038/srep12007.

Shore N.D. Darolutamide (ODM-201) for the treatment of prostate cancer. Expert Opin. Pharmacother. 2017;18:945–952. doi: 10.1080/14656566.2017.1329820.

Graff J.N., Baciarello G., Armstrong A.J. et al Efficacy and safety of enzalutamide in patients 75 years or older with chemotherapy‐naive metastatic castration‐resistant prostate cancer: results from PREVAIL. Ann Oncol 2016; 27: 286–294.

Morgans A.K., Shore N., Cope D. et al. Androgen receptor inhibitor treatments: Cardiovascular adverse events and comorbidity considerations in patients with non-metastatic prostate cancer. Urol Oncol. 2020 Sep 18:S1078-1439(20)30370-7. doi: 10.1016/j.urolonc.2020.08.003.

Di Nunno V., Mollica V., Santoni M. et al. New Hormonal Agents in Patients With Nonmetastatic Castration-Resistant Prostate Cancer: Meta-Analysis of Efficacy and Safety Outcomes. Clin Genitourin Cancer. 2019 Oct;17(5):e871-e877. doi: 10.1016/j.clgc.2019.07.001.

Crawford E.D., Stanton W., Mandair D. Darolutamide: An Evidenced-Based Review of Its Efficacy and Safety in the Treatment of Prostate Cancer. Cancer Manag Res. 2020 Jul 13;12:5667-5676. doi: 10.2147/CMAR.S227583.

Shore N., Zurth C., Fricke R. et al. Evaluation of Clinically Relevant Drug-Drug Interactions and Population Pharmacokinetics of Darolutamide in Patients with Nonmetastatic Castration-Resistant Prostate Cancer: Results of Pre-Specified and Post Hoc Analyses of the Phase III ARAMIS Trial. Target Oncol. 2019 Oct;14(5):527-539. doi: 10.1007/s11523-019-00674-0.

Zurth C., Koskinen M., Fricke R. et al. Drug–drug interaction potential of darolutamide: in vitro and clinical studies. Eur J Drug Metab Pharmacokinet. 2019 doi: 10.1007/s13318-019-00577-5.

Del Re M., Fogli S., Derosa L. et al. The role of drug-drug interactions in prostate cancer treatment: Focus on abiraterone acetate/prednisone and enzalutamide. Cancer Treat Rev. 2017 Apr;55:71-82. doi: 10.1016/j.ctrv.2017.03.001.

Benoist G.E., van Oort I.M., Smeenk S. et al. Drug-drug interaction potential in men treated with enzalutamide: Mind the gap. Br J Clin Pharmacol. 2018 Jan;84(1):122-129. doi: 10.1111/bcp.13425.

Duran I., Carles J., Bulat I. et al. Pharmacokinetic Drug-Drug Interaction of Apalutamide, Part 1: Clinical Studies in Healthy Men and Patients with Castration-Resistant Prostate Cancer. Clin Pharmacokinet. 2020 Sep;59(9):1135-1148. doi: 10.1007/s40262-020-00882-2.

Gibbons J.A., de Vries M., Krauwinkel W. et al. Pharmacokinetic Drug Interaction Studies with Enzalutamide. Clin Pharmacokinet. 2015 Oct;54(10):1057-69. doi: 10.1007/s40262-015-0283-1.

Pollock Y.G., Smith M.R., Saad F. et al. Predictors of falls and fractures in patients (pts) with nonmetastatic castration-resistant prostate cancer (nmCRPC) treated with apalutamide (APA) plus ongoing androgen deprivation therapy (ADT). J Clin Oncol. 2019;37:5025–5025.doi: 10.1200/JCO.2019.37.15_suppl.5025.

Barber M., Nguyen L.S., Wassermann J. et al. Cardiac arrhythmia considerations of hormone cancer therapies. Cardiovasc Res. 2019 Apr 15;115(5):878-894. doi: 10.1093/cvr/cvz020.

Creative Commons License

This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

© АННМО «Вопросы онкологии», Copyright (c) 2021