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Review
. 2020 Sep 7:12:8105-8114.
doi: 10.2147/CMAR.S227033. eCollection 2020.

PARP Inhibitors in Metastatic Prostate Cancer: Evidence to Date

Emily Nizialek  1 , Emmanuel S Antonarakis  1   2
Affiliations
Review

PARP Inhibitors in Metastatic Prostate Cancer: Evidence to Date

Emily Nizialek et al. Cancer Manag Res. .

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; homologous recombination; prostate cancer.

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Conflict of interest statement

Dr Antonarakis reports grants and personal fees from Janssen, personal fees from Astellas, grants and personal fees from Sanofi, grants and personal fees from Dendreon, personal fees from Pfizer, personal fees from Invitae, grants and personal fees from AstraZeneca, grants and personal fees from Clovis, grants and personal fees from Merck, grants from Johnson & Johnson, grants from Genentech, grants from Novartis, grants from Bristol Myers-Squibb; and also has patent (PCT/US2015/046806; US20170275673A1) on an AR-V7 biomarker technology, licensed to Qiagen. Dr Nizialek reports no financial disclosure to this work.

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