Multicenter phase 2 trial of olaparib without androgen deprivation therapy for high-risk biochemically recurrent prostate cancer following prostatectomy

The PARP inhibitor olaparib provides benefit in combination with hormonal therapies in patients with metastatic prostate cancer who harbor homologous recombination repair (HRR) alterations. Its efficacy in the absence of androgen deprivation therapy has not been tested. A phase 2 trial at four US centers evaluated olaparib monotherapy among genetically unselected patients with high-risk biochemically recurrent prostate cancer after radical prostatectomy. In this trial of 51 patients receiving olaparib, 13 patients (26%) had a confirmed 50% or higher decline in PSA level from baseline (PSA50 response). All PSA50 responses were seen in the HRR-positive group (13 of 27 patients; 48%). PSA50 response was observed in all 11 patients with BRCA2 alterations. The adverse effect profile was consistent with prior studies of olaparib. The authors conclude that olaparib without androgen deprivation has activity in certain patients with biochemically recurrent prostate cancer after radical prostatectomy.