New Insights into Therapy Selection for Metastatic Castration-Sensitive Prostate Cancer

The addition (intensification) of androgen pathway inhibitors (APIs; abiraterone, apalutamide, enzalutamide) or the chemotherapy agent docetaxel to androgen-deprivation therapy (ADT) is a standard of care for the management of metastatic castration-resistant prostate cancer based on level 1 evidence of improvement in overall survival (OS). Recent studies of “triplet” therapy — ADT plus docetaxel (D) plus either darolutamide or abiraterone — show further improvement in OS. Investigators now report a systemic review and meta-analyses of 10 randomized clinical trials of ADT intensification involving 11,043 patients with metastatic castration-resistant prostate cancer and 9 unique treatments options.

In the overall population, both the ADT/D/darolutamide and ADT/D/abiraterone triplet regimens were associated with a statistically significant improvement in OS compared with the ADT/D doublet regimen (hazard ratio, 0.68 and 0.75, respectively) but not compared with the ADT/apalutamide or ADT/abiraterone doublet regimens. In the subset of patients with low-volume disease, ADT/D/abiraterone triplet therapy did not significantly improve OS compared with any ADT/API doublet therapy or ADT/D. However, in patients with high-volume disease, ADT/D/abiritarone triplet therapy significantly improved OS compared with ADT/D doublet therapy but not compared with ADT/API doublet therapy.