Olaparib in Men With High-Risk Biochemically-Recurrent Prostate Cancer Following Radical Prostatectomy, With Integrated Biomarker Analysis

Summary

Olaparib has demonstrated preliminary efficacy in metastatic castration-resistant prostate cancer. In a trial of 49 evaluable patients treated with olaparib, 11 / 49 experienced a PSA response, and every patient with a radiographic response also had a PSA5 response. Ten of 11 responders had mutations in DNA repair genes. While PARP inhibition is showing promise in these initial studies, reserving its use for end-stage patients may not be the optimal timing for olaparib therapy in some patients. In addition, PARP enzymes function in roles beyond DNA repair, and specifically for prostate cancer are involved transcriptional regulation of the androgen receptor. PARP inhibition has not been tested in earlier disease states for prostate cancer.

Timeline

Start

2017-03-01

Primary completion

2023-05-24

Completion

2027-05-01

Publications

• Marshall CH, Teply BA, Lu J, Oliveira L, Wang H, Mao SS, Kelly WK, Paller CJ, Markowski MC, Denmeade SR, King S, Sullivan R, Davicioni E, Proudfoot JA, Eisenberger MA, Carducci MA, Lotan TL, Antonarakis ES. Olaparib Without Androgen Deprivation for High-Risk Biochemically Recurrent Prostate Cancer Following Prostatectomy: A Nonrandomized Controlled Trial. JAMA Oncol. 2024 Oct 1;10(10):1400-1408. doi: 10.1001/jamaoncol.2024.3074.

Drugs

Indications