Appropriate Selection of PARP Inhibitors in Ovarian Cancer

Abstract

Poly-ADP-ribose polymerase inhibitors (PARPi) are a class of anti-cancer drugs that target DNA repair pathways and have shown promising efficacy in patients with ovarian cancer in recent clinical trials. To date, there have been 9 FDA PARPi approvals/indications in ovarian cancer since 2014, highlighting the importance of this class of agents in the treatment of ovarian cancer. BRCA1/2-mutated tumors or other forms of homologous recombination deficient (HRD) tumors are particularly susceptible to PARP inhibition and have seen the greatest benefits of improvement in response rate and progression-free survival (PFS) in clinical trials. Patients with homologous recombination-proficient tumors also receive benefit, especially when a nice response to paltinum is noted, but to a lesser extent. PARP inhibitors now have FDA approval and indications in first-line and recurrent maintenance, and treatment. PARP inhibitor use as maintenance therapy in the front-line setting is now considered the standard of care in patients with BRCA1/2 mutations based on the SOLO-1/GOG-3004/ENGOT study. PARP inhibitors are also recommended per ASCO guidelines in all patients with ovarian cancer as front-line maintenance therapy based on the PRIMA/ENGOT-OV26/GOG-3012 trial. The combination of PARP inhibitor, olaparib, and the anti-angiogenesis inhibitor bevacizumab is also approved as maintenance therapy after front-line chemotherapy treatment in patients with HRD tumors and is an option for patients who have initiated bevacizumab with their chemotherapy treatment. PARPi are also FDA approved and can be utilized as a treatment in third-line and beyond in recurrent ovarian cancer patients with BRCA1/2 mutations and HRD tumors. In this review, we will cover in detail when PARP inhibitor use is appropriate in ovarian cancer, as well as the various clinical factors to take into consideration when selecting a PARP inhibitor regimen.

Keywords: BRCA; HRD; Niraparib; Olaparib; Ovarian cancer; PARP inhibitors; Rucaparib; Veliparib.