Wenzel Mike, Hoeh Benedikt, Chun Felix K H, Mandel Philipp
Klinik für Urologie, Universitätsklinikum Frankfurt, Theodor-Stern-Kai 7, 60590, Frankfurt, Deutschland.
Urologie. 2023 Apr;62(4):360-368. doi: 10.1007/s00120-023-02029-0. Epub 2023 Feb 10.
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.
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?
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).
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).
尽管几十年来,单纯雄激素剥夺疗法(ADT)一直是转移性激素敏感性前列腺癌(mHSPC)治疗的标准治疗方案(SOC),但新型激素疗法(雄激素受体靶向药物[ARTA])或多西他赛化疗的联合疗法最近已取代了单一ADT治疗。此外,目前已有ADT联合ARTA(阿比特龙/达罗他胺)和多西他赛化疗的三联疗法数据。
本综述探讨哪种疗法适用于哪种mHSPC患者。谁能从双联疗法中获益,谁能从三联疗法中获益?可能会出现哪些副作用?
与所有mHSPC(ARASENS)和原发性转移性高负荷(PEACE-1)mHSPC患者的ADT + 多西他赛疗法相比,ADT + 多西他赛 + 阿比特龙/达罗他胺组成的三联疗法可显著延长总生存期。在高负荷mHSPC患者中,ADT + 多西他赛 + 阿比特龙的特定三联组合可延长总生存期。在低负荷mHSPC患者中,仅观察到无进展生存期延长,而非总生存期延长。目前尚无关于由达罗他胺组成的三联疗法中高负荷与低负荷mHSPC分类的数据。三联疗法的副作用与双联疗法几乎相当,与典型的化疗相关副作用(中性粒细胞减少)和ARTA特异性副作用(阿比特龙)有关。
单纯ADT或ADT + 多西他赛不应再在mHSPC的一线治疗中发挥作用。因此,在有更多数据以及考虑患者特定特征(年龄、东部肿瘤协作组[ECOG]状态、转移负担、原发性/继发性转移疾病)之前,ADT + ARTA或ADT + ARTA + 多西他赛组成的疗法是目前的主要治疗选择。