Emerging drugs for the treatment of ovarian cancer: a focused review of PARP inhibitors

ABSTRACT

Introduction

Poly (ADP-ribose) polymerase (PARP) inhibitors have demonstrated significant anticancer activity in cancers harboring homologous recombination deficiency (HRD), exemplified by high grade serous ovarian cancer (HGSC). PARP inhibitors (PARPi) are being used in women with newly diagnosed ovarian cancer as well as in the recurrent setting. PARPi combination therapies are in development.

Areas covered

This review discusses the treatment of ovarian cancer, key PARPi clinical trials, mechanisms of action of PARPi, and novel PARPi combination regimens under investigation. PubMed and ClinicalTrials.gov were searched for PARPi trials. Active development was confirmed via PharmaProjects.

Expert opinion

PARPi have shown to improve progression-free survival (PFS) for women with HGSC as monotherapy in both frontline and recurrent maintenance settings and as monotherapy as treatment for recurrence. These benefits are greatest in HGSC with underlying HRD, in particular for those with deleterious BRCA mutations, and with the least benefit in cancers that are HR proficient (HRP) and BRCA wild-type (wt). Thus far, an improvement in overall survival has only been demonstrated in patients with BRCA mutated EOC treated with olaparib maintenance in the platinum sensitive recurrence setting. Novel combinations of PARPi are undergoing testing in an effort to increase PARPi efficacy in HRP or PARPi-resistant cancers.

KEYWORDS:

• BRCA
• DNA damage
• homologous recombination
• niraparib
• ovarian cancer
• olaparib
• PARP inhibitor
• rucaparib
• veliparib

Declaration of interest

UA Matulonis reports consulting work for Merck and Novartis. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

UA Matulonis is supported by the Breast Cancer Research Foundation.