Rucaparib: a new treatment option for ovarian cancer

ABSTRACT

Introduction: Approximately 50% of high-grade serous ovarian cancers present a deficiency in the pathways involved in homologous recombination (HR). PARP inhibitors prevent single-strand DNA damage repair and determine a progression of the defect towards double-strand breaks, which results in a process known as ‘synthetic lethality’.

Areas covered: In this review, the authors discuss the efficacy and toxicity of rucaparib either as a single agent or as a maintenance treatment for ovarian cancer. This includes the NGS Foundation Medicine evaluation of the role of this drug in the treatment algorithm of ovarian cancer. Moreover, perspectives on the future development of this drug are presented.

Expert opinion: The FDA has approved this drug for the treatment of recurrent BRCA-mutated ovarian cancers, which were previously treated with at least two chemotherapies and has accepted the supplemental new drug application for maintenance use in patients who respond to platinum-based chemotherapy via the Prescription Drug User Fee Act (PDUFA) on 6 April 2018. European Medicines Agency (EMA) approval in the same setting is awaited. The possibility of using PARP inhibitors as a maintenance therapy, as a front-line therapy to combat recurrence, and in combination with anti-angiogenic agents and immune-therapies appears to be of particular interest.

KEYWORDS:

• BRCA mutation
• ovarian cancer
• PARP inhibitor
• rucaparib

Declaration of interest

D Lorusso acted as the principal investigator of the ARIEL3 and ARIEL4 trials while I Sabatucci, G Maltese and S Lepori have all acted as sub-investigators for ARIEL3 and ARIEL4 trials. E Tripodi has also acted as a sub-investigator for the ARIEL4 trial. 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. One referee declares that they serve on the advisory boards of Clovis Oncology, Tesaro and AstraZeneca and has also been an investigator on rucaparib ovarian cancer trials.

Additional information

Funding

This manuscript has not been funded.