Dr. Rettig on the Evolving Use of Triplet Regimens in mHSPC

Matthew Rettig, MD, chief, hematology-oncology, VA Medical Center, professor of medicine and urology, David Geffen School of Medicine, University of California, Los Angeles (UCLA) Health, discusses the evolution of triplet therapy within the landscape of metastatic hormone-sensitive prostate cancer (mHSPC), as well as the importance of considering key prognostic factors when utilizing this approach.

Androgen-deprivation therapy (ADT) has been the standard therapeutic backbone for advanced mHSPC thus far, Rettig begins. Within the last decade, researchers have shown that the use of a second agent in combination with ADT in the upfront space, such as chemotherapy or novel hormonal agents, markedly improves survival outcomes, he details. Moreover, patients experience greater benefit when the combination regimen is used upfront in mHSPC, as opposed to being reserved for use after a patient progresses to metastatic castration-resistant prostate cancer, Rettig explains.

There is now an increased interest in the role of second-generation agents used in combination regimens for specific patient populations, Rettig continues. Several compelling data sets evaluatingthe use of triplet vs doublet regimens in prostate cancer have recently emerged, including the phase 3 ARASENS trial (NCT02799602), he says. In this trial, the novel hormonal-signaling agent darolutamide (Nubeqa) administered in combination with standard ADT and docetaxel reduced the risk of death by 32.5% and elicited a consistent overall survival (OS) benefit vs placebo plus ADT and docetaxel in patients with mHSPC.

A retrospective analysis of patient outcomes from the ARASENS trial evaluating disease volume and risks status was presented at the 2023 Genitourinary Cancers Symposium. Results from this analysis indicated that OS benefit was similarly preserved regardless of patients' disease volume or de novo metastatic disease designation, Rettig states.

However, there is still debate over which patients may benefit most from triplet regimens, Rettig notes. Patients with more favorable prognostic features, such as low-volume or recurrent disease, may only need doublet therapy that contains a hormonal-signaling agent rather than a triplet, he explains. These questions remain unanswered and require further investigation, Rettig concludes.

Editor’s Note: Dr. Rettig reports serving as a consultant or in an advisory role for Ambrx, Amgen, Clovis Oncology, NKimmune, Roivant; he received research funding from Janssen, Medivation/Astellas, Novartis, Progenics; he has stock or ownership interests in Oncovalent Therapeutics, Survalent; he has leadership roles in Aravalent, Survalent.