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Olaparib as maintenance treatment for patients with platinum-sensitive relapsed ovarian cancer

Ledermann, JA; Pujade-Lauraine, E; (2019) Olaparib as maintenance treatment for patients with platinum-sensitive relapsed ovarian cancer. Therapeutic Advances in Medical Oncology , 11 pp. 1-18. 10.1177/1758835919849753. Green open access

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Abstract

Poly (ADP-ribose) polymerase (PARP) inhibitors were developed with the intention of treating patients with homologous recombination repair deficiency (HRD), specifically for patients with tumours that harbour a BRCA mutation (BRCAm). Evidence from clinical trials to date has demonstrated that patients with a BRCAm derive the greatest benefit from PARP inhibitors. However, clinical studies have also shown that PARP inhibitors provide benefit to women with ovarian cancer who do not have a BRCAm. The recent updated approvals of olaparib, niraparib and rucaparib by the US Food and Drug Administration and the European Medicines Agency for the treatment of all platinum-sensitive relapsed (PSR) ovarian-cancer populations, regardless of their BRCAm status, support this. Long-term tolerability and efficacy of olaparib have been demonstrated in patients both with and without a BRCAm, with 13% of patients receiving maintenance olaparib for at least 5 years in one study, which is unprecedented in the relapsed ovarian-cancer setting (versus 1% on placebo). Further studies should be performed to elucidate which non-BRCAm patients are deriving benefit and what molecular processes are enabling this, so that patients continue to receive optimal treatment for their disease. Here, we review clinical and molecular markers of HRD, the long-term clinical safety and efficacy of PARP inhibitors in ovarian cancer, with a focus on olaparib and the current approved indications for PARP inhibitors, as well as guidance on treatment decisions for patients with PSR ovarian cancer.

Type: Article
Title: Olaparib as maintenance treatment for patients with platinum-sensitive relapsed ovarian cancer
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1177/1758835919849753
Publisher version: https://doi.org/10.1177%2F1758835919849753
Language: English
Additional information: © The Author(s), 2019. Article reuse guidelines: sagepub.com/journalspermissions. Creative Commons Non Commercial CC BY-NC: This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (http://www.creativecommons.org/licenses/by-nc/4.0/).
Keywords: niraparib, olaparib, PARP inhibitor, platinum-sensitive relapsed ovarian cancer, rucaparib, targeted therapy
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > CRUK Cancer Trials Centre
URI: https://discovery.ucl.ac.uk/id/eprint/10076915
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