When is the Best Time to Use PARP Inhibitors for Maintenance?

Poly ADP ribose polymerase (PARP) inhibitors have led to a step change in the management of advanced ovarian cancer following the first approval of these inhibitors in 2014. PARP is an enzyme needed for DNA repair and its inhibition results in the accumulation of single-strand DNA breaks. PARP inhibitors were initially hypothesized to have maximum efficacy in ovarian cancer with BRCA1/2 mutations or homologous recombination (HR) deficiency (HRD) ) given the role of these pathways in repairing double-stranded DNA breaks. The accumulation of both single-strand and double-strand breaks would result in synthetic lethality and preferential cancer cell cytotoxicity with BCRA1/2 mutations and HRD being a predictive biomarker of response. Here we present data that patients with recurrent ovarian cancer will benefit from PARP inhibitors, given as maintenance therapy irrespective of BRCA or HR status. This has been shown with olaparib, niraparib, and rucaparib; all three PARP inhibitors are licensed for the treatment of recurrent ovarian cancer following a response to platinum-based therapy in both BRCA-mutant and wild-type patients.