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

by Selleckchem | Jun 15 2023

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.

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Title: The Evolving Treatment Paradigm for Metastatic Castrate-Sensitive Prostate Cancer: Reviewing Triplet Therapy and Addressing Knowledge Gaps

Abstract: The landscape of metastatic castrate-sensitive prostate cancer (mCSPC) treatment has rapidly advanced in recent years, introducing multiple life-prolonging therapies. Various phase-three trials have shown a survival benefit with upfront triplet therapy combining androgen deprivation therapy (ADT), docetaxel chemotherapy, and either abiraterone acetate or darolutamide, compared to ADT plus docetaxel alone. However, crucial questions regarding the incremental benefit of docetaxel, optimal timing of androgen receptor pathway inhibitors (ARPI), patient selection for triplet therapy, and the role of clinical and genomic biomarkers remain unanswered. Real-world data reveal suboptimal treatment intensification, with many patients receiving ADT alone, highlighting implementation challenges. This article reviews phase-three trial data related to triplet therapy in mCSPC, discusses remaining knowledge gaps, and outlines ongoing studies that could reshape the treatment paradigm. Furthermore, a simplified algorithm based on current evidence is proposed to aid clinicians in selecting appropriate treatment strategies in daily practice.

Introduction: Background on the treatment landscape for metastatic castrate-sensitive prostate cancer (mCSPC)
Overview of approved life-prolonging therapies, including docetaxel chemotherapy and androgen receptor pathway inhibitors (ARPI) in combination with androgen deprivation therapy (ADT)

Conclusion:

Summary of key points discussed

Emphasis on the need for further research and collaboration to address knowledge gaps

Anticipation of paradigm shifts in the near future

This article aims to provide clinicians with an up-to-date understanding of the evolving treatment landscape for mCSPC, focusing on triplet therapy. By reviewing existing evidence and highlighting knowledge gaps, it serves as a guide for clinicians to make informed treatment decisions while considering ongoing research efforts that may shape future treatment approaches.