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Review
. 2023 Apr;62(4):360-368.
doi: 10.1007/s00120-023-02029-0. Epub 2023 Feb 10.

[Androgen deprivation therapy plus chemotherapy ± androgen receptor-targeting agents for metastatic hormone-sensitive prostate cancer]

[Article in German]
Mike Wenzel  1 , Benedikt Hoeh  2 , Felix K H Chun  2 , Philipp Mandel  3
Affiliations
Review

[Androgen deprivation therapy plus chemotherapy ± androgen receptor-targeting agents for metastatic hormone-sensitive prostate cancer]

[Article in German]
Mike Wenzel et al. Urologie. 2023 Apr.

Abstract
in English, German

Background: Although androgen deprivation therapy (ADT) alone has been the standard of care (SOC) in the treatment of metastatic hormone-sensitive prostate cancer (mHSPC) for decades, combination therapies of novel hormone therapy (androgen receptor-targeting agents [ARTA]) or docetaxel chemotherapy have more recently replaced single ADT treatment. In addition, data for triplet therapies with ADT plus ARTA (abiraterone/darolutamide) and docetaxel chemotherapy are now available.

Objectives: The present review addresses the question which therapy is suitable for which mHSPC patient. Who benefits from doublet therapy and which patient from triplet therapy? Which side effects can be expected?

Results: Triplet therapy consisting of ADT + docetaxel + abiraterone/darolutamide resulted in a significantly longer overall survival compared to therapy consisting of ADT + docetaxel of all mHSPC (ARASENS) and primary metastatic high-volume (PEACE-1) mHSPC patients. In the setting of high-volume mHSPC, prolonged overall survival is seen for the specific triplet combination of ADT + docetaxel + abiraterone. In the low-volume mHSPC setting, only an extended progression-free survival but not overall survival was observed. Data regarding the classification of high- vs. low-volume mHSPC for the triplet therapy consisting of darolutamide are currently not available. Side effects with triplet therapies are almost comparable with those of doublet therapies and relate to typical chemotherapy-associated (neutropenia) and ARTA-specific side effects (abiraterone).

Conclusion: ADT alone or ADT + docetaxel should no longer play a role in first-line therapy for mHSPC. Accordingly, therapy consisting of ADT + ARTA or ADT + ARTA + docetaxel represents the current primary treatment option pending further data and regarding patient-specific characteristics (age, ECOG status, metastatic burden, primary/secondary metastatic disease).

Zusammenfassung: HINTERGRUND: Nachdem die alleinige Androgendeprivationstherapie (ADT) lange Zeit die Goldstandardbehandlung des metastasierten hormonsensitiven Prostatakarzinoms (mHSPC) war, wurde diese in den letzten Jahren durch Doublet-Kombinationstherapien aus ADT + erweiterte Hormontherapie (ARTA, „androgen receptor targeted agent“) oder ADT + Docetaxel-Chemotherapie abgelöst. Erstmals stehen nun Daten aus Triplet-Kombinationstherapien aus ADT + ARTA (Abirateron/Darolutamid) + Docetaxel-Chemotherapie zur Verfügung.

Fragestellung: Welcher mHSPC-Patient profitiert von einer „Doublet“- vs. „Triplet-Kombinationstherapie“ und welches Nebenwirkungsspektrum ist jeweils zu erwarten?

Ergebnisse: Die aktuellen Triplet-Therapien (ADT + Docetaxel + Abirateron/Darolutamid) zeigen eine Verlängerung des Gesamtüberlebens gegenüber der Doublet-Therapie aus ADT + Docetaxel aller mHSPC (ARASENS) bzw. primär metastasierten „High-volume-“ (PEACE-1) mHSPC-Patienten. Im Setting des High-volume-mHSPC zeigt sich dieser positive Gesamtüberlebenseffekt explizit für die Triplet-Kombination aus ADT + Docetaxel + Abirateron. Beim Low-volume-mHSPC zeigt sich dieser Effekt lediglich für das progressionsfreie Überleben – jedoch nicht für das Gesamtüberleben. Ähnliche Darolutamid‑/Triplet-Kombinationstherapie’ Daten (High- vs. Low-volume-mHSPC) liegen aktuell nicht vor. Die Nebenwirkungsraten von „Triplet- vs. Doublet-Kombinationstherapie“ sind nur leicht erhöht und v. a. auf typische Chemotherapie-assoziierte (Neutropenie) und Androgenrezeptorantagonisten (ARTA)-spezifische Nebenwirkungen (Abirateron) zurückzuführen.

Zusammenfassung: Die ADT-Mono- und die „Doublet-Kombinationstherapie“ aus ADT + Docetaxel sollten in der Erstlinientherapie beim mHSPC keine Rolle mehr spielen. Bis zum Vorliegen weiterführender Daten über den Zusatznutzen der „Triplet-Kombinationstherapie“ in relevanten Subgruppen, stellen die Kombinationstherapien aus ADT + ARTA bzw. ADT + ARTA + Docetaxel in Abhängigkeit patientenspezifischer Charakteristika (Alter, ECOG [Eastern Cooperative Oncology Group], Metastasenlast, primäre/sekundäre Metastasierung) die aktuelle primären Therapieoptionen dar.

Keywords: Abiraterone; Combination therapy; Darolutamide; Docetaxel; Metastasis, neoplasm; Triplet therapy; mHSPC.

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