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PARP Inhibitors in Metastatic Prostate Cancer: Evidence to Date

Authors Nizialek E, Antonarakis ES

Received 15 July 2020

Accepted for publication 15 August 2020

Published 7 September 2020 Volume 2020:12 Pages 8105—8114


Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 4

Editor who approved publication: Dr Chien-Feng Li

Emily Nizialek,1 Emmanuel S Antonarakis1,2

1Department of Oncology, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD, USA; 2Department of Urology, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD, USA

Correspondence: Emmanuel S Antonarakis
Department of Oncology, Sidney Kimmel Comprehensive Cancer Center at John Hopkins, Baltimore, MD 21287, USA
Tel +1 410-502-8341
Fax +1 410-614-7287

Abstract: Poly (ADP-ribose) polymerase inhibitors (PARPi) are a unique class of antineoplastic agents that function by inducing synthetic lethality. Synthetic lethality occurs when PARPi and either another agent or an underlying genetic alteration together lead to overwhelming DNA damage and ultimately cell death. PARPi first showed promise as a cancer therapy in patients with BRCA1/2 mutations and have become part of standard treatment for breast and ovarian cancer. In prostate cancer, two PARPi, rucaparib and olaparib, have been FDA approved for the treatment of metastatic castration-resistant prostate cancer (mCRPC). While both agents are approved for tumors with BRCA1/2 alterations, for olaparib the indication is also expanded to patients with 12 other homologous recombination deficiency (HRD) gene alterations including ATM and PALB2. PARPi differ in their pharmacokinetics and pharmacodynamics, and additional studies are being conducted with niraparib, veliparib, and talazoparib in prostate cancer. While PARPi are fairly well tolerated, common toxicities include hematologic (anemia/thrombocytopenia) and gastrointestinal effects (nausea/vomiting). Ongoing studies are being conducted combining PARPi with other agents in patients with and without HRD alterations. Early data are promising for the combination of PARPi with second-generation antiandrogens and with immunotherapy. As additional trials are developed and reported, the hope is that the patient population who may benefit from PARPi will continue to expand.

Keywords: PARP inhibitor, prostate cancer, homologous recombination

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