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

Abstract

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.

Identifying Suitable Patients for Overcoming Androgen Deprivation Monotherapy in De Novo Metastatic Hormone-Sensitive Prostate Cancer

“…Several pivotal studies have emerged, demonstrating notable survival gains with the introduction of new medications such as abiraterone, enzalutamide, and apalutamide, thereby establishing a new standard of care for mHSPC [7]. Furthermore, there has been increasing attention on triplet treatment approaches involving androgen deprivation therapy (ADT) and androgen receptor-targeted agents (ARTAs) in combination with docetaxel [8]. ARTAs, designed to specifically target the androgen receptor, represent a novel class of treatments for prostate cancer, notable for their oral formulation, which often eliminates the need for hospitalization.…”

“…Recent advancements in prostate cancer therapy have culminated in the development of triplet therapy, as evidenced by trials such as PEACE-1, investigating abiraterone, and ARASENS, evaluating darolutamide [8]. Triplet therapy entails a combination of ADT with docetaxel, supplemented by the addition of an ARTA.…”