Systemic Triple Therapy in Metastatic Hormone-Sensitive Prostate Cancer (mHSPC): Ready for Prime Time or Still to Be Explored?

SIMPLE SUMMARY: Currently, a combination therapy of standard androgen deprivation therapy (ADT) plus docetaxel or androgen receptor-axis-targeted therapy is the gold standard for metastatic hormone-sensitive prostate cancer (mHSPC) treatment. Compared to ADT monotherapy, combination treatment prolongs overall survival by at least 18 months. The latest data has shown that triple treatment with standard ADT plus docetaxel plus abiraterone is superior to standard ADT plus docetaxel. Ongoing clinical trials are investigating triple therapy protocols by affecting diverse signaling pathways that are pivotal in prostate cancer. In this review, we will explore if triple therapy has the potential to be the new standard for mHSPC treatment in the near future. ABSTRACT: For decades, mono androgen deprivation therapy (ADT) has been the gold standard for metastatic hormone-sensitive prostate cancer (mHSPC) treatment. Several studies have been published within the last seven years demonstrating a significant survival advantage by combination treatment with standard ADT plus docetaxel or androgen receptor-axis-targeted therapy (ARAT) compared to ADT monotherapy. As a result, overall survival can be prolonged by at least 18 months. Recently published congress data of the PEACE-1 study suggests that in the future, triple therapy might be the new gold standard. In addition to this study, which has shown that triple treatment with standard ADT plus docetaxel plus abiraterone is superior to standard ADT plus docetaxel, several other phase III triple therapy studies are currently ongoing. The different modes of action that are investigated reach from AR-targeting over mitotic inhibition and immunotherapy to PARP and AKT inhibition. In this review we will explore if triple therapy has the potential to be the new standard for mHSPC treatment in the near future.