Dr Dreicer on the Potential Role of Triplet Therapy in De Novo Metastatic Prostate Cancer

Robert Dreicer, MD, director, Solid Tumor Oncology, Division of Hematology/Oncology, professor of Medicine and Urology, deputy director, University of Virginia Cancer Center, discusses the use of triplet therapy in the first-line management of de novo metastatic prostate cancer.

The potential role of frontline triplet therapies in prostate cancer is an area of ongoing investigation and debate, Dreicer states.

Data from the phase 3 PEACE1 trial (NCT01957436) demonstrated that the addition of abiraterone acetate (Zytiga) and radiation therapy to androgen deprivation therapy (ADT) and docetaxel improved both overall survival (OS) and radiographic progression-free survival. Notably, this trial only enrolled patients with de novo metastatic castrate-resistant prostate cancer, Dreicer says.

Similarly, the phase 3 ARASENS trial (NCT02799602) evaluated darolutamide (Nubeqa) plus standard ADT and docetaxel vs placebo plus ADT and docetaxel, demonstrating that the triplet regimen reduced the risk of death. Moreover, the triplet regimen provided an OS benefit in patients with metastatic hormone-sensitive prostate cancer.

A post-hoc analysis on the effect of disease volume and risk status on patient benefit was published and presented at the 2023 Genitourinary Cancers Symposium, Dreicer adds, showing that patients with high-volume, high-risk disease experience sub-optimal responses vs low-volume or low-risk patients. Although this was an all-comer study, a large percentage of patients enrolled had de novo metastatic disease, Dreicer emphasizes. This presentation was identified as a poor prognostic factor. 

As a majority of efficacy and safety data on the use of triplet regimens was collected from patients with de novo presentation, the utilization of this approach in patients should be highly considered, Dreicer states. Regarding ADT intensification, treatment with an ADT and an androgen receptor inhibitor should be considered for patients who do not have specific contraindications for this approach, he concludes. 

Editor's Note: Dr Dreicer serves as a consultant or in an advisory role for Astellas Pharma, AstraZeneca, AVEO, Bayer, Exelixis, Genzyme, Gilead Sciences, Hengrui Pharmaceutical, Hinova Pharmaceuticals, Janssen, Merck, Pfrizer, and Tavanta Therapeutics; he has received institutional research funding from Bristol-Myers Squibb, Exelixis and Seagen.