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Delivering widespread BRCA testing and PARP inhibition to patients with ovarian cancer

Key Points

  • Poly [ADP-ribose] polymerase (PARP) inhibitors are an effective maintenance therapy in patients with platinum-sensitive ovarian cancer and also in those who have received multiple lines of previous treatment

  • BRCA-mutation status provides important information for the identification of patients that are most likely to benefit from treatment with PARP inhibitors

  • BRCA-mutation testing should be offered to patients with ovarian cancer on the basis of histological subtype, and should not be limited to those with a family and/or personal history of BRCA-related malignancy

  • Additional tests to identify patients that would benefit from PARP inhibitors, including the use of homologous recombination deficiency (HRD) gene signatures and assessing genomic loss of heterozygosity seem promising

  • Data from ongoing clinical trials will help define how best to select patients with ovarian cancer for treatment with PARP inhibitors

Abstract

The treatment of patients with ovarian cancer is rapidly changing following the success of poly [ADP-ribose] polymerase (PARP) inhibitors in clinical trials. Olaparib is the first PARP inhibitor to be approved by the EMA and FDA for BRCA-mutated ovarian cancer. Germ line BRCA mutation status is now established as a predictive biomarker of potential benefit from treatment with a PARP inhibitor; therefore, knowledge of the BRCA status of an individual patient with ovarian cancer is essential, in order to guide treatment decisions. BRCA testing was previously offered only to women with a family or personal history of breast and/or ovarian cancer; however, almost 20% of women with high-grade serous ovarian cancer are now recognized to harbour a germ line BRCA mutation, and of these, >40% might not have a family history of cancer and would not have received BRCA testing. A strategy to enable more widespread implementation of BRCA testing in routine care is, therefore, necessary. In this Review, we summarize data from key clinical trials of PARP inhibitors and discuss how to integrate these agents into the current treatment landscape of ovarian cancer. The validity of germ line BRCA testing and other promising biomarkers of homologous-recombination deficiency will also be discussed.

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Figure 1: Putative anticancer mechanisms of action of PARP inhibitors.

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Acknowledgements

We would like to thank the Royal Marsden Hospital and Institute of Cancer Research National Institute for Health Research (NIHR) Biomedical Research Centre for Cancer (BRC).

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A.G. and S.B. researched data for this article, all authors made a substantial contribution to discussions of content, A.G. and S.B. wrote the manuscript, and all authors reviewed and/or edited the manuscript prior to submission.

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Correspondence to Susana Banerjee.

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A.G. declares that she has received honoraria from AstraZeneca. S.K. is on the advisory boards of AstraZeneca and Tesaro. S.B. is on the advisory boards of Astrazeneca and Clovis, but declares that she has received no personal financial remuneration as a result of these activities.

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George, A., Kaye, S. & Banerjee, S. Delivering widespread BRCA testing and PARP inhibition to patients with ovarian cancer. Nat Rev Clin Oncol 14, 284–296 (2017). https://doi.org/10.1038/nrclinonc.2016.191

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