Triplet Therapy in Metastatic Castrate Sensitive Prostate Cancer (mCSPC)-A Potential New Standard of Care

The treatment paradigm for metastatic castrate-sensitive prostate cancer (mCSPC) has evolved rapidly in the past decade with the approval of several life-prolonging therapies including docetaxel chemotherapy and multiple androgen receptor pathway inhibitors (ARPI) in combination with androgen deprivation therapy (ADT). Recently reported phase-three trials have demonstrated a survival benefit of upfront triplet therapy with ADT, docetaxel plus either abiraterone acetate or darolutamide when compared to ADT plus docetaxel alone. However, multiple questions including the incremental benefit of docetaxel to a combination of ADT and ARPI, the timing of ARPI, optimal patient selection for triplet therapy and clinical and genomic biomarkers still remain to be answered. Moreover, real-world data suggest suboptimal treatment intensification with many patients treated with ADT alone highlighting challenges in implementation. In this article, we review the phase-three data associated with triplet therapy in mCSPC. We also discuss the knowledge gaps that exist despite the completion of these studies and how ongoing studies are likely to change the paradigm in the near future. Finally, we provide a simple algorithm based on current data that clinicians can use in daily practice to select patients for appropriate treatment strategies.

Automated summary

The treatment paradigm for metastatic castrate-sensitive prostate cancer (mCSPC) has rapidly evolved with the approval of life-prolonging therapies. However, there are still unanswered questions regarding the benefit of docetaxel in combination with androgen deprivation therapy (ADT) and androgen receptor pathway inhibitors (ARPI), optimal patient selection, and clinical and genomic biomarkers. Real-world data also suggest suboptimal treatment intensification. This article reviews phase-three data on triplet therapy in mCSPC and highlights knowledge gaps and ongoing studies that may change the treatment paradigm.