Highlights in Prostate Cancer from ASCO GU 2022

Abstract

VIEWPOINTS MAGNITUDE: Niraparib plus AAP significantly improved clinical outcomes as first-line therapy for mCRPC with HRR gene alterationsUp to 30% of patients with prostate cancer have defects in the homologous recombination repair (HRR) genes such as BRCA1/2, ATM and CHEK2, 1 rendering these tumors highly sensitive to poly(ADP-ribose) polymerase (PARP) inhibitors (i) like olaparib or niraparib. Blocking androgen receptor (AR) signaling in patients receiving androgen-deprivation therapy (ADT) activates PARP signaling, resulting in synthetic lethality upon PARP inhibition, as demonstrated in preclinical models. 2 Promising results were previously reported from phase II trials on olaparib in combination with abiraterone acetate (AA), as well as niraparib monotherapy, in patients with metastatic castration-resistant prostate cancer (mCRPC). 3,4 Recent data also showed that olaparib yielded improved survival in the phase III PROfound trial in patients with mCRPC who had disease progression while receiving a new hormonal agent (NHA) like enzalutamide or abiraterone. 5,6 Based on these positive results, the MAGNITUDE and PROpel trials have been initiated.