Androgen deprivation therapy plus chemotherapy +/- androgen receptor-targeting agents for metastatic hormone-sensitive prostate cancer

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).