Triplet or Doublet Therapy in Metastatic Hormone-sensitive Prostate Cancer Patients: An Updated Network Meta-analysis Including ARANOTE Data

Abstract

The treatment landscape for metastatic hormone-sensitive prostate cancer (mHSPC) has been extended by another phase 3 randomized control trial (ARANOTE) demonstrating favorable outcomes of a doublet therapy combining the androgen receptor pathway inhibitor (ARPI) darolutamide with androgen deprivation therapy (ADT) over ADT monotherapy. Owing to differences in trial designs, patient enrollment, and most notably different control treatment regimens, we hereby present an updated network meta-analysis (NMA) embedding the doublet therapy with darolutamide within the current treatment regimens. In NMA-derived ranking, darolutamide and ADT showed similar oncological efficacy to the already known doublet therapies for progression-free survival (p = 0.49). These findings were consistent when solely doublet treatments, including apalutamide, enzalutamide, or darolutamide, were stratified according to disease volume. Overall survival (OS) data in ARANOTE are very immature, with up to date no significant differences in OS between the doublet regimen and the control group (hazard ratio: 0.81; 95% confidence interval: 0.59-1.12). The combination of darolutamide and ADT is likely-with the requirement of additional follow-up-to become another standard of care regimen for mHSPC following approval in the future. PATIENT SUMMARY: The phase 3 ARANOTE trial has shown the combination of darolutamide and androgen deprivation therapy (ADT) to have favorable outcomes for metastatic hormone-sensitive prostate cancer (mHSPC) over ADT monotherapy. This combination therapy was as effective as the already known doublet therapies for progression free-survival, and had a very favorable safety and toxicity profile. Following approval, the combination of darolutamide and ADT may become another standard of care regimen for mHSPC.

Keywords: ARANOTE; Abiraterone; Androgen receptor pathway inhibitor; Apalutamide; Darolutamide; Doublet therapy; Enzalutamide; Hormone sensitive; Metastatic hormone-sensitive prostate cancer; Metastatic prostate cancer.