PARP Inhibitors in Ovarian Cancer: A Review

Abstract

Poly(ADP-ribose) polymerase (PARP) inhibitors (PARPis) have transformed the ovarian cancer (OC) treatment landscape. This narrative review provides a comprehensive overview of data for the PARPis olaparib, niraparib, and rucaparib in patients with OC and discusses their role in disease management, with a focus on the use of PARPis as maintenance therapy in the United States (US). Olaparib was the first PARPi to be approved as first-line maintenance monotherapy in the US, with maintenance niraparib subsequently approved in the first-line setting. Data also support the efficacy of rucaparib as first-line maintenance monotherapy. PARPi maintenance combination therapy (olaparib plus bevacizumab) also provides benefit in patients with newly diagnosed advanced OC whose tumors tested positive for homologous recombination deficiency (HRD). Biomarker testing is critical in the newly diagnosed setting to identify patients most likely to benefit from PARPi maintenance therapy and guide treatment decisions. Clinical trial data support the use of PARPis (olaparib, niraparib, rucaparib) as second-line or later maintenance therapy in patients with platinum-sensitive relapsed OC. Although distinct differences in tolerability profile were observed between PARPis, they were generally well tolerated, with the majority of adverse events managed by dose modification. PARPis had no detrimental effect on patients' health-related quality of life. Real-world data support the use of PARPis in OC, although some differences between PARPis are apparent. Data from trials investigating novel combination strategies, such as PARPis plus immune checkpoint inhibitors, are awaited with interest; the optimal sequencing of novel therapies in OC remains to be established.

Fig. 1

US approval of PARP inhibitors for use in patients with OC*. *The trial(s) on which approval was based is shown in parentheses. 1L first-line, 3L+ third-line or later, 4L+ fourth-line or later, BRCAm BRCA1 and/or BRCA2 mutation, g germline, HRD homologous recombination deficiency, OC ovarian cancer, PARP poly(ADP-ribose) polymerase, PSR platinum-sensitive relapsed, +ve positive

Fig. 2

Proposed treatment algorithm for newly diagnosed ovarian cancer. Adapted from DiSilvestro et al. Maintenance treatment of newly diagnosed advanced ovarian cancer: time for a paradigm shift? Cancers 2021;13(22):5756 [118] (https://doi.org/10.3390/cancers13225756), an open access article distributed under the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). *Germline BRCAm testing should be offered to all patients with epithelial ovarian cancer at diagnosis, with tumor testing for somatic BRCAm for patients in whom a germline BRCAm is not detected; ^†Olaparib and niraparib approved in the US; ^‡Niraparib approved in the US; ^§Olaparib + bev approved in the US; ^ǁBev approved in the US. bev bevacizumab, BRCAm BRCA1 and/or BRCA2 mutation, CR complete response, HRD homologous recombination deficiency, IV intravenous, NACT neoadjuvant therapy, NED no evidence of disease, PARPi poly(ADP-ribose) polymerase inhibitor, PBC platinum-based chemotherapy, PDS primary debulking surgery, PR partial response, q3w every 3 weeks

Fig. 3

Proposed treatment algorithm for platinum-sensitive relapsed ovarian cancer. *Olaparib, niraparib, and rucaparib approved in the US (niraparib approved in patients with a germline BRCAm and rucaparib approved in patients with a BRCAm); ^†Bev approved in the US. bev bevacizumab, BRCAm BRCA1 and/or BRCA2 mutation, IV intravenous, PARPi poly(ADP-ribose) polymerase inhibitor, PBC platinum-based chemotherapy, q3w every 3 weeks