Radium-223 in the Modern Treatment of Metastatic Castration-resistant Prostate Cancer
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Abstract
The objective: is to determine the current role of radium-223 in the emergence of new options in the treatment of patients with metastatic castration-resistant prostate cancer.
Materials and methods. Studies of ERA-223 and ALSYMPCA have identified the role of radium-223 in the treatment of prostate cancer and its impact on human health.
Results. In one such study, ERA-223, it was shown that the combination of abiraterone with radium-223 did not increase survival without symptomatic skeletal events compared with abiraterone plus placebo. In addition, a higher incidence of bone fractures was observed with the combination of abiraterone and radium-223, especially in patients not receiving osteomodulators (denosumab or zoledronic acid). These results have led to some changes in the indications for the use of radium-223 in Europe and more careful attention to the state of bone structure in patients with prostate cancer.
An overview of expert recommendations for the prevention and treatment of bone events, as well as the consequences of prolonged targeted therapy in patients with metastatic prostate cancer, which may improve the results of general and cancer-specific survival. Radium-223 has been shown to be an important option for patients with castration-resistant prostate cancer with bone metastases, and monitoring and maintaining bone health is an important factor in prostate cancer patients. It is established that the treatment of this category of patients should begin with androge n deprivation therapy.
Conclusions. A review of the recommendations of urologists, oncologists and radiation oncologists in Europe, who specialize in the treatment of patients with advanced prostate cancer, to maintain bone health, treatment consequences and the role of radium-223 in the treatment of prostate cancer. Based on the analysis of the use of radium-223 in the current treatment of CRPD, preventive measures to maintain bone health are recommended, as well as side effects based on clinical experience.
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References
Belderbos B.P.S., de Wit R., Lolkema M.P.J., Mathijssen R.H.J., van Soest R.J. Novel treatment options in the management of metastatic castration-naive prostate cancer: which treatment modality to choose? Annals of Oncology 2019; vol. 30, issue 10: 1591–1600.
James N.D., de Bono J.S., Spears M.R., et al. Abiraterone for prostate cancer not previously treated with hormone therapy. N Engl J Med 2017; 377: 338–351.
James N.D., Sydes M., Clarke N.M., et al. Addition of docetaxel, zoledronic acid, or both to first-line long-term hormone therapy in prostate cancer (STAMPEDE): survival results from an adaptive, multiarm, multistage, platform randomized controlled trial. Lancet 2016; 387: 1163–1177.
Sweeney C.J., Chen Y.H., Carducci M., et al. Chemohormonal therapy in metastatic hormone-sensitive prostate cancer. N Engl J Med 2015; 373: 737–746.
Parker C.C., James N.D., Brawley C.D., et al. Radiotherapy to the primary tumor for newly diagnosed, metastatic prostate cancer (STAMPEDE): a randomized controlled phase 3 trial. Lancet 2018; 392: 2353–2366.
Ryan C.J., Smith M.R., de Bono J.S., et al. Abirateronin metastatic prostate cancer without previous chemotherapy. N Engl J Med 2013; 368: 138–148.
Beer T.M., Armstrong A.J., Rathkopf D.E., et al. Enzalutamide in metastatic prostate cancer before chemotherapy. N Engl J Med 2014; 371: 424–433.
Hussain M., Fizasi K.,SaadF.,et al. Enzalutamide in men with nonmetastatic, castratio-resistant prostate cancer. N Engl J Med 2018; 378: 2465–2474.
Smith M.R., Antonarakis E.S., Ryan C.J., et al. Phase 2 study of the safety and antitumor activity of apalutamide (ARN-509), a potent androgen receptor antagonist, in the high-risk nonmetastasis castration-resistant prostate cancer cohort. Eur Urol 2016; 70: 963–970.
Tannock I.F., de Wit R., Berry W.R., et al. Docetaxel plus prednisone or mitoxantrone for advanced prostate cancer. N Engl J Med 2004; 351: 1502–1512.
de Bono J.S., Oudard S., Ozguroglu M., et al. Prednisone plus cabazitaxel or mitoxantrone for metastatic castrationresistant prostate cancer progressing after docetaxel treatment : a randomized open-label trial. Lancet 2010; 376: 1147–1154.
Parker C., Nilsson S., Heinrich D., et al. Alpha emitter radium-223 and survival in metastatic prostate cancer. N Engl J Med 2012; 369: 213–223.
Fizazi K, Carducci M., Smith M.R., et al. Denozumab versus zoledronic acid for the treatment of bone metastases in men with castration-resistent prostate cancer: a randomized, double-blind study. Lancet 2011; 377: 813–822.
Saad F, Gleason D. M., Murray R., et al. A randomized, placebo-controlled trial of zoledronic acid in patients with hormone-refractory metastatic prostate carcinoma. J Natl Cancer Inst 2002; 94: 1458–1468.
Beer T.M., Armstrong A.J., Rathkopf D.E., et al. Enzalutamide in men with chemotherapy-naive metastatic castration-resistentprostate cancer: extended analysis of the phase 3 PREVAIL study. Eur Urol 2017;71:151–156.
Ryan C.J., Smith M.R., Fizazi K., et al. Abiraterone acetate plus prednisone versus placebo plus prednisone in chemotherapy-naïve men with metastatic castration-resistant prostate cancer (COU-AA-302): final overall survival analysis of a randomized, double-blind, placebo-controlled phase 3 study. Lancet Oncol 2015; 16: 152–160.
Smith M.,Parker C., Saad F., et al. Addition of radium-223 to abiraterone acetate and prednisone or prednisone in patients with castration-resistent prostate cancer and bone metastases (ERA 223): a randomized, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol 2019; 20: 408–419.
Bayer A.G. Xofigo (radium-223) [summary of product characteristics]. 2018 (www.ema.europa.eu/documents/product-information/xofigo-eparproduct-information_en.pdf).
Brechbiel M.W. Targeted alpha-therapy: past, present, future? Dalton Trans 2007; 43: 4918–4928.
Suominen M.I., Fagerlund R.M., Rissanen J.P., et al.Radium-223 inhibits osseous prostate cancer growth by dual targeting of cancer cells and bone microenvironment in mouse models. Clin Cancer Res 2017; 23: 4335–4346.
Parker C.C., Coleman R.E., Sartor O., et al.Tree-year safety of radium-223 dichloride in patients with castration-resistant prostate cancer and symptomatic bone metastases from phase 3 randomise-dalpharadin in symptomatic prostate cancers trial. Eur Urol 2017;73:427–35.
Nilsson S., Cislo P, Sartor O., et al. Patient-reported quality-of-life analysis of radium-223 dichloride from the phase ІІІ ALSYMPCA study. Ann Oncol 2016; 27: 868–74.
Cherny NI, Dafni U, Bogaerts J, et al. ESMO-magnitude of clinical benefit scale version 1.1. Ann Oncol 2017; 28: 2340–66.
Stein M.N., Patel N., Bershadskiy A., Sokoloff A., Singer E.A. Androgen synthesis ingibitors in the treatment of castration-resistant prostate cancer. Asian J Androl 2014; 16: 387–400.
Saad F., Carles J.,GillessenS., et al. Radium-223 and concomitant therapies in patients with metastatic castration-resistant prostate cancer: an international, early access, open-label, single-arm phase 3b trial. Lancet Oncol 2016; 17: 1306–16.
Ryan C. Apollo 14 and the lessens from fractures. 2018 (https://www.urotoday.com/center-of-excellence/mcrpctreatment/from-the-editor/108224-apollo-14-and-the-lessons-from-fractures.html).
Morote J., Morin J.P., Orsola A., et al. Prevalence of osteoporosis during long-term androgen deprivation therapy in patients with prostate cancer. Urology 2007; 69: 500–504.
van Staa T.P., Leufkens H.G.M., Albenhim L., Zhang B., Cooper C. Oral corticosteroids and fracture risk: relationship to daily and cumulative doses. Rheumatology (Oxford) 2000; 39: 1383–1389.
Janssen Biotech, Inc. Zytiga (abiraterone acetate) [prescribing information]. 2018; www.zytiga.com.
Astellas Pharma US, Inc. Xtandy (enzalutamide) [prescribing information]. 2018; www.xtandy.com
Janssen Products. Erleada (apalutamide) [prescribing information]. 2018; www.erleada.com.
Ndibe C., Wang C.G., Sonpavde G. Corticosteroids in the management of prostate cancer: a critical review. Curr Trea Options Oncol 2015; 16; 6.
Chin R.Y., Ima-Nirvana S. Sex steroids and bone health status in men. Int J Endocrinol 2012; 2012: 208719.
Fizazi K., Shore N., Tammela T.L., et al. Darolutamide in nonmetastatic, castration-resistant prostate cancer. N Engl J Med 2019; ([Epub ahead of print]) http://doi.org/10.1056/NEJMoa1815671
Cianferotti L., Bertoldo F., Carini M., et al. The prevention of fragility fractures in patients with non-metastatic prostate cancer: a position statement by the international osteoporosis foundation. Oncotarget 2017; 8: 75646–75663.
Pezaro C., Omlin A., Lorente D., et al. Visceral disease in castration-resistant prostate cancer. EurUrol 2014; 65: 270–273.
Suva L.J., Washam C., Nicolas R.W., Griffin R.J. Bone metastasis: mechanisms and tharapuetic opportunities. Nat Rev Endocrinol 2017; 7: 208–218.
Berruti A., Dogliotti L., Bitossi R., et al. Incidence of skeletal complications in patients with bone metastatic prostate cancer and hormone refractory disease: predictive role of bone resorption and formation markers evaluated at baseline. J Urol 2000; 164: 1248–1253.
Roghmann F., Antczak C., McKay R.R., et al. The burden of skeletal-related events in patients with prostate cancer and bone metastasis.UrolOncol 2015; 33: 17.e9–17.e18.
McKay R., Haider B., Duh M.S., et al. Impact of symptomatic skeletal events on health-care resource utilization and quality of life among patients with castrationresistant prostate cancer and bone metastases. Prostate Cancer Prostatic Dis. 2017; 20: 276–282.
Howard L.E., De Hoedt A.M., Aronson W.J., et al. Do skeletal-related events predict overall survival in men with metastatic castration-resistant prostate cancer? Prostate Cancer Prostatic Dis. 2016; 19: 380–384.
Miller K., Heinrich D., OSullivan J.M., et al. Radium-223 (Ra-223) therapy after abiraterone (Abi): analysis of symptomatic skeletal events (SSEs) in an international early access program (iEAP) in patients (pts) with metastatic castrationresistant prostate cancer (mCRPC). Ann Oncol 2018; 29: mdy284.033.
Sternberg C.N., Tombal B., Miller K., et al. Use of bone health agents (BHAs) in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) treated with radium-223 (Ra-223) after abiraterone (Abi): an interim rewiew of REASSURE. Ann Oncol 2018; 29: mdy284.035.
Coleman R., Body J.J., Aapro M., Hadji P., Herrstedt J. on behalf of the EGWG. Bone health in cancer patients: ESMO clinical practice guidelines. Ann Oncol 2014; 25: iii124–iii137.
Cornford P., Bellmunt J, Bolla M., et al. EAU-ESTRO-SIOG guidelines on prostate cancer. Part II: treatment of relapsing, metastatic, and castration-resistant prostate cancer. EurUrol 2017; 71: 630–642.
Logothetis C., Basch E., Molsna A., et al. Effect of abiraterone acetate and prednisone compared with placebo and prednisone on pain control and skeletal-related events in patients with metastatic castration-resistant prostate cancer: exploratory analysis of data from the COUAA-301 randomised trial. Lancet Oncol 2012; 13: 1210–1217.
Fizazi K, Scher H.I., Miller K., et al. Effect of enzalutamide on time to first skeletal-related event, pain, and quality of life in men with castration-resistant prostate cancer: results from the randomized, phase 3 AFFIRM trial. Lancet Oncol 2014; 15: 1147–1156.
Sartor O., Coleman R., Nilsson S., et al. Effect of Radium-223 dichloride on symptomatic skeletal events in patients with castration-resistant prostate cancer and bone metastases: results from phase 3, double-blind, randomized trial. Lancet Oncol 2014; 15: 738–746.
Saad F., Shore N., Van Poppel H., et al. Impact of bone-target therapies in chemotherapy-naive metastatic, castration-resistant prostate cancer patients treated with abiraterone acetate: post hoc analysis of studyCOU-AA-302. Eur Urol 2015; 68: 570–577.
Bultijnck R., Surcel C., Ploussard G., et al. Practice patterns compared with evidence-based strategies for the management of androgen deprivation therapy-induced side effects in prostate cancer patients: results of a European web-based survey. Eur Urol Focus 2016; 2: 514–521.
Kanis J.A., Johnell O, Oden A, Johansson H, McCloskey E. FRAX® and the assessment of fracture probability in men and women from UK. Osteoporos Int 2008; 19: 385–97.
