Medikamentöse Tumortherapie des mHSPC: Double- oder Tripletherapie: wer, wann und wie?

Zusammenfassung

Die alleinige Androgendeprivation (ADT) zur Therapie des metastasierten hormonsensitiven Prostatakarzinoms (mHSPC) stellt mittlerweile eine Ausnahme dar. Die derzeitige Standardtherapie des mHSPC besteht aus einer Kombination: entweder ADT + neuartigen Hormontherapie (NHT) oder ADT + Chemotherapie. Aufgrund neuester Studiendaten und einer entsprechenden Zulassung (in Deutschland) nimmt die dreifache Kombination bestehend aus ADT + NHT + Chemotherapie Einzug in die Therapie des mHSPC. Die komplexer werdende mHSPC-Therapie erfordert die prätherapeutische Einteilung in ein „low“ vs. „high risk“, „low“ vs. „high volume“ und synchron vs. metachron metastasiertes HSPC. Zudem muss das Nebenwirkungsprofil der einzelnen Optionen beachtet und insbesondere eingeschätzt werden, ob der Patient Chemotherapie-fit vs. -unfit ist. Diese Übersicht gibt einen prägnanten Überblick über die relevanten Studien sowie die entsprechenden derzeit gültigen Empfehlungen und Zulassungen für Deutschland.

Abstract

At present, androgen deprivation therapy (ADT) as monotherapy for metastatic hormone-sensitive prostate cancer (mHSPC) should be an exception. The new standard of care is a doublet combination consisting of ADT + a new hormonal agent (NHA) or ADT + chemotherapy. Contemporary investigations even recommend a triplet therapy consisting of ADT + NHA + chemotherapy for selected mHSPC patients. The current evolution of mHSPC therapy demands a pretherapeutic classification of mHSPC: “low” vs. “high risk”, “low” vs. “high volume” and synchronous vs. metachronous mHSPC. Additionally, attention should be paid to the drug specific side effects and especially whether the patient is fit for chemotherapy. This article gives a concise overview of the key clinical trials, current guideline recommendations and drug approvals for Germany.

Schlüsselwörter

ADT - mHSPC - Doubletherapie - Tripletherapie - NHT

Keywords

ADT - mHSPC - Doublet Therapy - Triplet Therapy - NHA

Publikationsverlauf

Eingereicht: 07. Juni 2023

Angenommen nach Revision: 13. Juli 2023

Artikel online veröffentlicht:
22. August 2023

• Literatur

• 1 Weiner AB, Matulewicz RS, Eggener SE. et al. Increasing incidence of metastatic prostate cancer in the United States (2004–2013). Prostate Cancer Prostatic Dis 2016; 19: 395-397
• 2 Fizazi K, Tran N, Fein L. et al. Abiraterone plus Prednisone in Metastatic, Castration-Sensitive Prostate Cancer. N Engl J Med 2017; 377: 352-360
• 3 Sweeney CJ, Chen YH, Carducci M. et al. Chemohormonal Therapy in Metastatic Hormone-Sensitive Prostate Cancer. N Engl J Med 2015; 373: 737-746
• 4 S3 Leitlinie Prostatakarzinom Version 6.2. Zugriff am 17. Mai 2023 unter: https://www.leitlinienprogramm-onkologie.de/fileadmin/user_upload/Downloads/Leitlinien/Prostatatkarzinom/Version_6/LL_Prostatakarzinom_Langversion_6.2.pdf
• 5 EAU Guidelines Prostate Cancer. Zugriff am 17. Mai 2023 unter: https://uroweb.org/guidelines/prostate-cancer
• 6 Fachinformation Abirateron. Zugriff am 17. Mai 2023 unter: https://www.ema.europa.eu/en/documents/product-information/zytiga-epar-product-information_de.pdf
• 7 Fachinformation Enzalutamid. Zugriff am 17. Mai 2023 unter: https://www.xtandi.de/sites/default/files/2022–06/xtandi_40–80mg_f.-tbl._fachinfo_-_stand_mai_2022.pdf?dl=1
• 8 Fachinformation Apalutamid. Zugriff am 17. Mai 2023 unter: https://static.janssen-emea.com/sites/default/files/Germany/SMPC/DE-PL-0021.pdf?tracked
• 9 Fachinformation Docetaxel. Zugriff am 17. Mai 2023 unter: https://www.accord-healthcare.de/sites/default/files/2022–07/Accord_Fachinformation_Docetaxel.pdf
• 10 Fizazi K, Tran N, Fein L. et al. 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 2019; 20: 686-700
• 11 James ND, de Bono JS, Spears MR. et al. Abiraterone for Prostate Cancer Not Previously Treated with Hormone Therapy. N Engl J Med 2017; 377: 338-351
• 12 James ND, Clarke NW, Cook A. et al. Abiraterone acetate plus prednisolone for metastatic patients starting hormone therapy: 5-year follow-up results from the STAMPEDE randomised trial (NCT00268476). Int J Cancer 2022; 151: 422-434
• 13 Davis ID, Martin AJ, Stockler MR. et al. Enzalutamide with Standard First-Line Therapy in Metastatic Prostate Cancer. N Engl J Med 2019; 381: 121-131
• 14 Sweeney CJ, Martin AJ, Stockler MR. et al. Testosterone suppression plus enzalutamide versus testosterone suppression plus standard antiandrogen therapy for metastatic hormone-sensitive prostate cancer (ENZAMET): an international, open-label, randomised, phase 3 trial. Lancet Oncol 2023; 24: 323-334
• 15 Armstrong AJ, Szmulewitz RZ, Petrylak DP. et al. 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 2019; 37: 2974-2986
• 16 Armstrong AJ, Azad AA, Iguchi T. et al. Improved Survival With Enzalutamide in Patients With Metastatic Hormone-Sensitive Prostate Cancer. J Clin Oncol 2022; 40: 1616-1622
• 17 Chi KN, Agarwal N, Bjartell A. et al. Apalutamide for Metastatic, Castration-Sensitive Prostate Cancer. N Engl J Med 2019; 381: 13-24
• 18 Chi KN, Chowdhury S, Bjartell A. et al. Apalutamide in Patients With Metastatic Castration-Sensitive Prostate Cancer: Final Survival Analysis of the Randomized, Double-Blind, Phase III TITAN Study. J Clin Oncol 2021; 39: 2294-2303
• 19 Kyriakopoulos CE, Chen YH, Carducci MA. et al. Chemohormonal Therapy in Metastatic Hormone-Sensitive Prostate Cancer: Long-Term Survival Analysis of the Randomized Phase III E3805 CHAARTED Trial. J Clin Oncol 2018; 36: 1080-1087
• 20 James ND, Sydes MR, Clarke NW. 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 randomised controlled trial. Lancet 2016; 387: 1163-1177
• 21 Clarke NW, Ali A, Ingleby FC. et al. Addition of docetaxel to hormonal therapy in low- and high-burden metastatic hormone sensitive prostate cancer: long-term survival results from the STAMPEDE trial. Erratum in: Ann Oncol 2020; 31: 442. Ann Oncol 2019; 30: 1992-2003
• 22 Fachinformation Darolutamid. Zugriff am 17. Mai 2023 unter: https://www.ema.europa.eu/en/documents/product-information/nubeqa-epar-product-information_de.pdf
• 23 Smith MR, Hussain M, Saad F. et al. Darolutamide and Survival in Metastatic, Hormone-Sensitive Prostate Cancer. N Engl J Med 2022; 386: 1132-1142
• 24 Hussain M, Tombal B, Saad F. et al. Darolutamide Plus Androgen-Deprivation Therapy and Docetaxel in Metastatic Hormone-Sensitive Prostate Cancer by Disease Volume and Risk Subgroups in the Phase III ARASENS Trial. J Clin Oncol 2023; 41: 3595-3607
• 25 Fizazi K, Foulon S, Carles J. et al. 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 × 2 factorial design. Lancet 2022; 399: 1695-1707
• 26 Mori K, Mostafaei H, Sari Motlagh R. et al. Systemic therapies for metastatic hormone-sensitive prostate cancer: network meta-analysis. BJU Int 2022; 129: 423-433
• 27 Mandel P, Hoeh B, Wenzel M. et al. Triplet or Doublet Therapy in Metastatic Hormone-sensitive Prostate Cancer Patients: A Systematic Review and Network Meta-analysis. Eur Urol Focus 2023; 9: 96-105
• 28 Francini E, Gray KP, Xie W. et al. Time of metastatic disease presentation and volume of disease are prognostic for metastatic hormone sensitive prostate cancer (mHSPC). Prostate 2018; 78: 889-895
• 29 Sathianathen NJ, Pan HYC, Lawrentschuk N. et al. Emergence of triplet therapy for metastatic castration-sensitive prostate cancer: An updated systematic review and network meta-analysis. Urol Oncol 2023; 41: 233-239
• 30 Roy S, Sayyid R, Saad F. et al. Addition of Docetaxel to Androgen Receptor Axis-targeted Therapy and Androgen Deprivation Therapy in Metastatic Hormone-sensitive Prostate Cancer: A Network Meta-analysis. Eur Urol Oncol 2022; 5: 494-502
• 31 Yanagisawa T, Rajwa P, Thibault C. et al. Androgen Receptor Signaling Inhibitors in Addition to Docetaxel with Androgen Deprivation Therapy for Metastatic Hormone-sensitive Prostate Cancer: A Systematic Review and Meta-analysis. Eur Urol 2022; 82: 584-598
• 32 Hofman MS, Lawrentschuk N, Francis RJ. et al. Prostate-specific membrane antigen PET-CT in patients with high-risk prostate cancer before curative-intent surgery or radiotherapy (proPSMA): a prospective, randomised, multicentre study. Lancet 2020; 395: 1208-1216
• 33 Barbato F, Fendler WP, Rauscher I. et al. PSMA-PET for the assessment of metastatic hormone-sensitive prostate cancer volume of disease. J Nucl Med 2021; 62: 1747-1750
• 34 Mattana F, Muraglia L, Rajwa P. et al. Metastatic Sites' Location and Impact on Patient Management After the Introduction of Prostate-specific Membrane Antigen Positron Emission Tomography in Newly Diagnosed and Biochemically Recurrent Prostate Cancer: A Critical Review. Eur Urol Oncol 2023; 6: 128-136
• 35 Mourey L, Boyle HJ, Roubaud G. et al. Efficacy and safety of abiraterone acetate plus prednisone and androgen deprivation therapy +/- docetaxel in older patients (≥70 years), with de novo metastatic-castration sensitive prostate cancer, compared to younger patients (<70 years): The PEACE-1 trial. Journal of Clinical Oncology 2023; 41 (Suppl. 06) 20-20