Clinical Utility of Olaparib in the Treatment of Metastatic Castration-Resistant Prostate Cancer: A Review of Current Evidence and Patient Selection [Corrigendum]

Abstract

1Department of Medicine, Division of Hematology and Oncology, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA; 2Department of Surgery, Division of Cancer Biology and Therapeutics, Biomedical Sciences, and Pathology and Laboratory Medicine, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA; 3Department of Surgery, Division of Urology, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA; 4Section of Urology, Durham VA Medical Center, Durham, NC, USA Abstract: Metastatic castration-resistant prostate cancer (mCRPC) is an aggressive and fatal disease with a median survival of 36 months. With the advent of genetic sequencing to identify individual genomic profiles and acquired tumor-specific pathways, targeted therapies have revolutionized cancer treatment, including the treatment strategy in mCRPC. Poly(adenosine 5ʹdiphosphate) ribose polymerase inhibitors (PARPi) are oral drugs that target mutations in the homologous recombination repair (HRR) pathway, which are found in approximately 27% of prostate cancer patients. In May 2020, the first PARP inhibitor, olaparib, was approved by the US Food and Drug Administration for men with mCRPC with HHR gene mutations based on the findings of the Phase III PROfound trial that showed improved overall survival in men with mCRPC who received olaparib and whose disease had progressed on a novel hormonal agent. This review summarizes the current evidence and clinical utility of olaparib as treatment in men with mCRPC. We describe the mechanism of action of PARPi, key clinical trials of olaparib in men with mCRPC, and ongoing Phase II and III clinical trials investigating olaparib in combination therapy and as front-line therapy in mCRPC.