Skip to main content
Erschienen in: Die Urologie 5/2023

27.04.2023 | Prostatakarzinom | CME

Neuartige Hormontherapien beim fortgeschrittenen Prostatakarzinom

verfasst von: Dr. med. August Sigle, Christian Gratzke, Markus Grabbert

Erschienen in: Die Urologie | Ausgabe 5/2023

Einloggen, um Zugang zu erhalten

Zusammenfassung

Die Systemtherapie des fortgeschrittenen Prostatakarzinoms (PCa) hat im vergangenen Jahrzehnt eine regelrechte Revolution erlebt. In allen Krankheitsstadien kam es sowohl zur Zulassung neuer Substanzen wie auch zu einer zunehmenden Intensivierung der Therapie. Hierbei stehen weiterhin und insbesondere Substanzen mit einer Wirkung auf die Androgenrezeptorachse im Mittelpunkt. In der vorliegenden Übersichtsarbeit werden zugelassene Therapieoptionen für das metastasierte hormonsensitive PCa (mHSPC), das nichtmetastasierte (nmCRPC) sowie das metastasierte kastrationsrefraktäre PCa (mCRPC) zusammengefasst. Ein besonderer Fokus liegt auf den neuartigen Hormontherapeutika. Anhand aktueller Studiendaten werden zudem mögliche Dreifachkombinationen beim mHSPC sowie Therapiesequenzoptionen und neue zielgerichtete Substanzen beim mCRPC vorgestellt.
Literatur
1.
Zurück zum Zitat Huggins C, Hodges CV (1972) Studies on prostatic cancer. I. The effect of castration, of estrogen and androgen injection on serum phosphatases in metastatic carcinoma of the prostate. CA Cancer J Clin 22(4):232–240CrossRefPubMed Huggins C, Hodges CV (1972) Studies on prostatic cancer. I. The effect of castration, of estrogen and androgen injection on serum phosphatases in metastatic carcinoma of the prostate. CA Cancer J Clin 22(4):232–240CrossRefPubMed
3.
Zurück zum Zitat Fizazi K, Tran N, Fein L, Matsubara N, Rodriguez-Antolin A, Alekseev BY et al (2019) Abiraterone acetate plus prednisone in patients with newly diagnosed high-risk metastatic castration-sensitive prostate cancer (LATITUDE): final overall survival analysis of a randomised, double-blind, phase 3 trial. Lancet Oncol 20(5):686–700CrossRefPubMed Fizazi K, Tran N, Fein L, Matsubara N, Rodriguez-Antolin A, Alekseev BY et al (2019) Abiraterone acetate plus prednisone in patients with newly diagnosed high-risk metastatic castration-sensitive prostate cancer (LATITUDE): final overall survival analysis of a randomised, double-blind, phase 3 trial. Lancet Oncol 20(5):686–700CrossRefPubMed
5.
Zurück zum Zitat Fizazi K, Shore N, Tammela TL, Ulys A, Vjaters E, Polyakov S et al (2020) Nonmetastatic, castration-resistant prostate cancer and survival with darolutamide. N Engl J Med 383(11):1040–1049CrossRefPubMed Fizazi K, Shore N, Tammela TL, Ulys A, Vjaters E, Polyakov S et al (2020) Nonmetastatic, castration-resistant prostate cancer and survival with darolutamide. N Engl J Med 383(11):1040–1049CrossRefPubMed
6.
Zurück zum Zitat Halabi S, Jiang S, Terasawa E, Garcia-Horton V, Ayyagari R, Waldeck AR et al (2021) Indirect comparison of darolutamide versus apalutamide and enzalutamide for nonmetastatic castration-resistant prostate cancer. J Urol 206(2):298–307CrossRefPubMed Halabi S, Jiang S, Terasawa E, Garcia-Horton V, Ayyagari R, Waldeck AR et al (2021) Indirect comparison of darolutamide versus apalutamide and enzalutamide for nonmetastatic castration-resistant prostate cancer. J Urol 206(2):298–307CrossRefPubMed
9.
Zurück zum Zitat Fizazi K, Tran N, Fein L, Matsubara N, Rodriguez-Antolin A, Alekseev BY et al (2017) Abiraterone plus prednisone in metastatic, castration-sensitive prostate cancer. N Engl J Med 377(4):352–360CrossRefPubMed Fizazi K, Tran N, Fein L, Matsubara N, Rodriguez-Antolin A, Alekseev BY et al (2017) Abiraterone plus prednisone in metastatic, castration-sensitive prostate cancer. N Engl J Med 377(4):352–360CrossRefPubMed
10.
Zurück zum Zitat Sweeney CJ, Chen YH, Carducci M, Liu G, Jarrard DF, Eisenberger M et al (2015) Chemohormonal therapy in metastatic hormone-sensitive prostate cancer. N Engl J Med 373(8):737–746CrossRefPubMedPubMedCentral Sweeney CJ, Chen YH, Carducci M, Liu G, Jarrard DF, Eisenberger M et al (2015) Chemohormonal therapy in metastatic hormone-sensitive prostate cancer. N Engl J Med 373(8):737–746CrossRefPubMedPubMedCentral
11.
Zurück zum Zitat Smith MR, Hussain M, Saad F, Fizazi K, Sternberg CN, Crawford ED et al (2022) Darolutamide and survival in metastatic, hormone-sensitive prostate cancer. N Engl J Med 386(12):1132–1142CrossRefPubMedPubMedCentral Smith MR, Hussain M, Saad F, Fizazi K, Sternberg CN, Crawford ED et al (2022) Darolutamide and survival in metastatic, hormone-sensitive prostate cancer. N Engl J Med 386(12):1132–1142CrossRefPubMedPubMedCentral
12.
Zurück zum Zitat Fizazi K, Foulon S, Carles J, Roubaud G, McDermott R, Flechon A et al (2022) Abiraterone plus prednisone added to androgen deprivation therapy and docetaxel in de novo metastatic castration-sensitive prostate cancer (PEACE-1): a multicentre, open-label, randomised, phase 3 study with a 2 x 2 factorial design. Lancet 399(10336):1695–1707CrossRefPubMed Fizazi K, Foulon S, Carles J, Roubaud G, McDermott R, Flechon A et al (2022) Abiraterone plus prednisone added to androgen deprivation therapy and docetaxel in de novo metastatic castration-sensitive prostate cancer (PEACE-1): a multicentre, open-label, randomised, phase 3 study with a 2 x 2 factorial design. Lancet 399(10336):1695–1707CrossRefPubMed
13.
Zurück zum Zitat Thomas C, Baunacke M, Erb HHH, Fussel S, Erdmann K, Putz J et al (2022) Systemic triple therapy in metastatic hormone-sensitive prostate cancer (mHSPC): ready for prime time or still to be explored? Cancers (Basel) 14(1):8CrossRef Thomas C, Baunacke M, Erb HHH, Fussel S, Erdmann K, Putz J et al (2022) Systemic triple therapy in metastatic hormone-sensitive prostate cancer (mHSPC): ready for prime time or still to be explored? Cancers (Basel) 14(1):8CrossRef
14.
Zurück zum Zitat Chi KN, Protheroe A, Rodriguez-Antolin A, Facchini G, Suttman H, Matsubara N et al (2018) Patient-reported outcomes following abiraterone acetate plus prednisone added to androgen deprivation therapy in patients with newly diagnosed metastatic castration-naive prostate cancer (LATITUDE): an international, randomised phase 3 trial. Lancet Oncol 19(2):194–206CrossRefPubMed Chi KN, Protheroe A, Rodriguez-Antolin A, Facchini G, Suttman H, Matsubara N et al (2018) Patient-reported outcomes following abiraterone acetate plus prednisone added to androgen deprivation therapy in patients with newly diagnosed metastatic castration-naive prostate cancer (LATITUDE): an international, randomised phase 3 trial. Lancet Oncol 19(2):194–206CrossRefPubMed
15.
Zurück zum Zitat James ND, de Bono JS, Spears MR, Clarke NW, Mason MD, Dearnaley DP et al (2017) Abiraterone for prostate cancer not previously treated with hormone therapy. N Engl J Med 377(4):338–351CrossRefPubMedPubMedCentral James ND, de Bono JS, Spears MR, Clarke NW, Mason MD, Dearnaley DP et al (2017) Abiraterone for prostate cancer not previously treated with hormone therapy. N Engl J Med 377(4):338–351CrossRefPubMedPubMedCentral
16.
Zurück zum Zitat Hoyle AP, Ali A, James ND, Cook A, Parker CC, de Bono JS et al (2019) Abiraterone in “high-” and “low-risk” metastatic hormone-sensitive prostate cancer. Eur Urol 76(6):719–728CrossRefPubMed Hoyle AP, Ali A, James ND, Cook A, Parker CC, de Bono JS et al (2019) Abiraterone in “high-” and “low-risk” metastatic hormone-sensitive prostate cancer. Eur Urol 76(6):719–728CrossRefPubMed
17.
Zurück zum Zitat Chi KN, Agarwal N, Bjartell A, Chung BH, Pereira de Santana Gomes AJ, Given R et al (2019) Apalutamide for metastatic, castration-sensitive prostate cancer. N Engl J Med 381(1):13–24CrossRefPubMed Chi KN, Agarwal N, Bjartell A, Chung BH, Pereira de Santana Gomes AJ, Given R et al (2019) Apalutamide for metastatic, castration-sensitive prostate cancer. N Engl J Med 381(1):13–24CrossRefPubMed
18.
Zurück zum Zitat Davis ID, Martin AJ, Stockler MR, Begbie S, Chi KN, Chowdhury S et al (2019) Enzalutamide with standard first-line therapy in metastatic prostate cancer. N Engl J Med 381(2):121–131CrossRefPubMed Davis ID, Martin AJ, Stockler MR, Begbie S, Chi KN, Chowdhury S et al (2019) Enzalutamide with standard first-line therapy in metastatic prostate cancer. N Engl J Med 381(2):121–131CrossRefPubMed
19.
Zurück zum Zitat Armstrong AJ, Szmulewitz RZ, Petrylak DP, Holzbeierlein J, Villers A, Azad A et al (2019) ARCHES: a randomized, phase III study of androgen deprivation therapy with enzalutamide or placebo in men with metastatic hormone-sensitive prostate cancer. J Clin Oncol 37(32):2974–2986CrossRefPubMedPubMedCentral Armstrong AJ, Szmulewitz RZ, Petrylak DP, Holzbeierlein J, Villers A, Azad A et al (2019) ARCHES: a randomized, phase III study of androgen deprivation therapy with enzalutamide or placebo in men with metastatic hormone-sensitive prostate cancer. J Clin Oncol 37(32):2974–2986CrossRefPubMedPubMedCentral
21.
Zurück zum Zitat Fendler WP, Weber M, Iravani A, Hofman MS, Calais J, Czernin J et al (2019) Prostate-specific membrane antigen ligand positron emission tomography in men with nonmetastatic castration-resistant prostate cancer. Clin Cancer Res 25(24):7448–7454CrossRefPubMed Fendler WP, Weber M, Iravani A, Hofman MS, Calais J, Czernin J et al (2019) Prostate-specific membrane antigen ligand positron emission tomography in men with nonmetastatic castration-resistant prostate cancer. Clin Cancer Res 25(24):7448–7454CrossRefPubMed
22.
Zurück zum Zitat Smith MR, Saad F, Chowdhury S, Oudard S, Hadaschik BA, Graff JN et al (2018) Apalutamide treatment and metastasis-free survival in prostate cancer. N Engl J Med 378(15):1408–1418CrossRefPubMed Smith MR, Saad F, Chowdhury S, Oudard S, Hadaschik BA, Graff JN et al (2018) Apalutamide treatment and metastasis-free survival in prostate cancer. N Engl J Med 378(15):1408–1418CrossRefPubMed
24.
Zurück zum Zitat Fizazi K, Shore N, Tammela TL, Ulys A, Vjaters E, Polyakov S et al (2019) Darolutamide in nonmetastatic, castration-resistant prostate cancer. N Engl J Med 380(13):1235–1246CrossRefPubMed Fizazi K, Shore N, Tammela TL, Ulys A, Vjaters E, Polyakov S et al (2019) Darolutamide in nonmetastatic, castration-resistant prostate cancer. N Engl J Med 380(13):1235–1246CrossRefPubMed
25.
Zurück zum Zitat Fizazi K, Shore ND, Tammela T, Ulys A, Vjaters E, Polyakov S et al (2020) Overall survival (OS) results of phase III ARAMIS study of darolutamide (DARO) added to androgen deprivation therapy (ADT) for nonmetastatic castration-resistant prostate cancer (nmCRPC). J Clin Oncol 38(15):5514CrossRef Fizazi K, Shore ND, Tammela T, Ulys A, Vjaters E, Polyakov S et al (2020) Overall survival (OS) results of phase III ARAMIS study of darolutamide (DARO) added to androgen deprivation therapy (ADT) for nonmetastatic castration-resistant prostate cancer (nmCRPC). J Clin Oncol 38(15):5514CrossRef
26.
Zurück zum Zitat Hussain M, Fizazi K, Saad F, Rathenborg P, Shore N, Ferreira U et al (2018) Enzalutamide in men with nonmetastatic, castration-resistant prostate cancer. N Engl J Med 378(26):2465–2474CrossRefPubMedPubMedCentral Hussain M, Fizazi K, Saad F, Rathenborg P, Shore N, Ferreira U et al (2018) Enzalutamide in men with nonmetastatic, castration-resistant prostate cancer. N Engl J Med 378(26):2465–2474CrossRefPubMedPubMedCentral
27.
Zurück zum Zitat Tombal B, Saad F, Penson D, Hussain M, Sternberg CN, Morlock R et al (2019) Patient-reported outcomes following enzalutamide or placebo in men with non-metastatic, castration-resistant prostate cancer (PROSPER): a multicentre, randomised, double-blind, phase 3 trial. Lancet Oncol 20(4):556–569CrossRefPubMed Tombal B, Saad F, Penson D, Hussain M, Sternberg CN, Morlock R et al (2019) Patient-reported outcomes following enzalutamide or placebo in men with non-metastatic, castration-resistant prostate cancer (PROSPER): a multicentre, randomised, double-blind, phase 3 trial. Lancet Oncol 20(4):556–569CrossRefPubMed
28.
Zurück zum Zitat Sternberg CN, Fizazi K, Saad F, Shore ND, De Giorgi U, Penson DF et al (2020) Enzalutamide and survival in nonmetastatic, castration-resistant prostate cancer. N Engl J Med 382(23):2197–2206CrossRefPubMed Sternberg CN, Fizazi K, Saad F, Shore ND, De Giorgi U, Penson DF et al (2020) Enzalutamide and survival in nonmetastatic, castration-resistant prostate cancer. N Engl J Med 382(23):2197–2206CrossRefPubMed
29.
Zurück zum Zitat Hird AE, Magee DE, Bhindi B, Ye XY, Chandrasekar T, Goldberg H et al (2020) A systematic review and network meta-analysis of novel androgen receptor inhibitors in non-metastatic castration-resistant prostate cancer. Clin Genitourin Cancer 18(5):343–350CrossRefPubMed Hird AE, Magee DE, Bhindi B, Ye XY, Chandrasekar T, Goldberg H et al (2020) A systematic review and network meta-analysis of novel androgen receptor inhibitors in non-metastatic castration-resistant prostate cancer. Clin Genitourin Cancer 18(5):343–350CrossRefPubMed
30.
Zurück zum Zitat Fizazi K, Scher HI, Molina A, Logothetis CJ, Chi KN, Jones RJ et al (2012) 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 13(10):983–992CrossRefPubMed Fizazi K, Scher HI, Molina A, Logothetis CJ, Chi KN, Jones RJ et al (2012) 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 13(10):983–992CrossRefPubMed
31.
Zurück zum Zitat Beer TM, Armstrong AJ, Rathkopf DE, Loriot Y, Sternberg CN, Higano CS et al (2014) Enzalutamide in metastatic prostate cancer before chemotherapy. N Engl J Med 371(5):424–433CrossRefPubMedPubMedCentral Beer TM, Armstrong AJ, Rathkopf DE, Loriot Y, Sternberg CN, Higano CS et al (2014) Enzalutamide in metastatic prostate cancer before chemotherapy. N Engl J Med 371(5):424–433CrossRefPubMedPubMedCentral
32.
Zurück zum Zitat Ryan CJ, Smith MR, Fizazi K, Saad F, Mulders PF, Sternberg CN et al (2015) Abiraterone acetate plus prednisone versus placebo plus prednisone in chemotherapy-naive men with metastatic castration-resistant prostate cancer (COU-AA-302): final overall survival analysis of a randomised, double-blind, placebo-controlled phase 3 study. Lancet Oncol 16(2):152–160CrossRefPubMed Ryan CJ, Smith MR, Fizazi K, Saad F, Mulders PF, Sternberg CN et al (2015) Abiraterone acetate plus prednisone versus placebo plus prednisone in chemotherapy-naive men with metastatic castration-resistant prostate cancer (COU-AA-302): final overall survival analysis of a randomised, double-blind, placebo-controlled phase 3 study. Lancet Oncol 16(2):152–160CrossRefPubMed
33.
Zurück zum Zitat Scher HI, Fizazi K, Saad F, Taplin ME, Sternberg CN, Miller K et al (2012) Increased survival with enzalutamide in prostate cancer after chemotherapy. N Engl J Med 367(13):1187–1197CrossRefPubMed Scher HI, Fizazi K, Saad F, Taplin ME, Sternberg CN, Miller K et al (2012) Increased survival with enzalutamide in prostate cancer after chemotherapy. N Engl J Med 367(13):1187–1197CrossRefPubMed
34.
Zurück zum Zitat Khalaf DJ, Annala M, Taavitsainen S, Finch DL, Oja C, Vergidis J et al (2019) Optimal sequencing of enzalutamide and abiraterone acetate plus prednisone in metastatic castration-resistant prostate cancer: a multicentre, randomised, open-label, phase 2, crossover trial. Lancet Oncol 20(12):1730–1739CrossRefPubMed Khalaf DJ, Annala M, Taavitsainen S, Finch DL, Oja C, Vergidis J et al (2019) Optimal sequencing of enzalutamide and abiraterone acetate plus prednisone in metastatic castration-resistant prostate cancer: a multicentre, randomised, open-label, phase 2, crossover trial. Lancet Oncol 20(12):1730–1739CrossRefPubMed
35.
Zurück zum Zitat Loriot Y, Bianchini D, Ileana E, Sandhu S, Patrikidou A, Pezaro C et al (2013) Antitumour activity of abiraterone acetate against metastatic castration-resistant prostate cancer progressing after docetaxel and enzalutamide (MDV3100). Ann Oncol 24(7):1807–1812CrossRefPubMed Loriot Y, Bianchini D, Ileana E, Sandhu S, Patrikidou A, Pezaro C et al (2013) Antitumour activity of abiraterone acetate against metastatic castration-resistant prostate cancer progressing after docetaxel and enzalutamide (MDV3100). Ann Oncol 24(7):1807–1812CrossRefPubMed
36.
Zurück zum Zitat de Wit R, de Bono J, Sternberg CN, Fizazi K, Tombal B, Wulfing C et al (2019) Cabazitaxel versus abiraterone or enzalutamide in metastatic prostate cancer. N Engl J Med 381(26):2506–2518CrossRefPubMed de Wit R, de Bono J, Sternberg CN, Fizazi K, Tombal B, Wulfing C et al (2019) Cabazitaxel versus abiraterone or enzalutamide in metastatic prostate cancer. N Engl J Med 381(26):2506–2518CrossRefPubMed
37.
Zurück zum Zitat Sartor O, de Bono J, Chi KN, Fizazi K, Herrmann K, Rahbar K et al (2021) Lutetium-177-PSMA-617 for metastatic castration-resistant prostate cancer. N Engl J Med 385(12):1091–1103CrossRefPubMedPubMedCentral Sartor O, de Bono J, Chi KN, Fizazi K, Herrmann K, Rahbar K et al (2021) Lutetium-177-PSMA-617 for metastatic castration-resistant prostate cancer. N Engl J Med 385(12):1091–1103CrossRefPubMedPubMedCentral
38.
Zurück zum Zitat Ohlmann CH, Jaschke M, Jaehnig P, Krege S, Gschwend J, Rexer H et al (2022) LHRH sparing therapy in patients with chemotherapy-naive, mCRPC treated with abiraterone acetate plus prednisone: results of the randomized phase II SPARE trial. Prostate Cancer Prostatic Dis 25(4):778–784CrossRefPubMedPubMedCentral Ohlmann CH, Jaschke M, Jaehnig P, Krege S, Gschwend J, Rexer H et al (2022) LHRH sparing therapy in patients with chemotherapy-naive, mCRPC treated with abiraterone acetate plus prednisone: results of the randomized phase II SPARE trial. Prostate Cancer Prostatic Dis 25(4):778–784CrossRefPubMedPubMedCentral
39.
Zurück zum Zitat de Bono J, Mateo J, Fizazi K, Saad F, Shore N, Sandhu S et al (2020) Olaparib for metastatic castration-resistant prostate cancer. N Engl J Med 382(22):2091–2102CrossRefPubMed de Bono J, Mateo J, Fizazi K, Saad F, Shore N, Sandhu S et al (2020) Olaparib for metastatic castration-resistant prostate cancer. N Engl J Med 382(22):2091–2102CrossRefPubMed
42.
Zurück zum Zitat Chi KN, Rathkopf DE, Smith MR, Efstathiou E, Attard G, Olmos D et al (2022) Phase 3 MAGNITUDE study: first results of niraparib (NIRA) with abiraterone acetate and prednisone (AAP) as first-line therapy in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) with and without homologous recombination repair (HRR) gene alterations. J Clin Oncol 40(6):12CrossRef Chi KN, Rathkopf DE, Smith MR, Efstathiou E, Attard G, Olmos D et al (2022) Phase 3 MAGNITUDE study: first results of niraparib (NIRA) with abiraterone acetate and prednisone (AAP) as first-line therapy in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) with and without homologous recombination repair (HRR) gene alterations. J Clin Oncol 40(6):12CrossRef
43.
Zurück zum Zitat Merseburger AS, Attard G, Astrom L, Matveev VB, Bracarda S, Esen A et al (2022) Continuous enzalutamide after progression of metastatic castration-resistant prostate cancer treated with docetaxel (PRESIDE): an international, randomised, phase 3b study. Lancet Oncol 23(11):1398–1408CrossRefPubMed Merseburger AS, Attard G, Astrom L, Matveev VB, Bracarda S, Esen A et al (2022) Continuous enzalutamide after progression of metastatic castration-resistant prostate cancer treated with docetaxel (PRESIDE): an international, randomised, phase 3b study. Lancet Oncol 23(11):1398–1408CrossRefPubMed
Metadaten
Titel
Neuartige Hormontherapien beim fortgeschrittenen Prostatakarzinom
verfasst von
Dr. med. August Sigle
Christian Gratzke
Markus Grabbert
Publikationsdatum
27.04.2023

Weitere Artikel der Ausgabe 5/2023

Die Urologie 5/2023 Zur Ausgabe

AUO

AUO

Aktuelles aus der DGU-Pressestelle

Aktuelles aus der DGU-Pressestelle

BvDU Kurz notiert

BvDU Kurz notiert