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Delivering widespread BRCA testing and PARP inhibition to patients with ovarian cancer
Angela George1,2, Stan Kaye2, Susana Banerjee2
1Cancer Genetics Unit, The Royal Marsden NHS Foundation, Fulham Road, London SW3 6JJ, UK.
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.
Insights
Poly [ADP-ribose] polymerase (PARP) inhibitors are transforming ovarian cancer treatment. Germ line BRCA mutation testing is crucial for identifying patients who benefit from PARP inhibitors like olaparib.
Area of Science:
- Oncology
- Genetics
- Pharmacology
Background:
- Ovarian cancer treatment is evolving with the advent of poly [ADP-ribose] polymerase (PARP) inhibitors.
- Olaparib, the first approved PARP inhibitor, targets BRCA-mutated ovarian cancer.
- Germ line BRCA mutation status is a key predictive biomarker for PARP inhibitor efficacy.
Purpose of the Study:
- To review clinical trial data on PARP inhibitors in ovarian cancer.
- To discuss the integration of PARP inhibitors into current ovarian cancer treatment paradigms.
- To explore the role of germ line BRCA testing and other biomarkers.
Main Methods:
- Review of key clinical trials involving PARP inhibitors.
- Analysis of current treatment guidelines and emerging data.
- Discussion of biomarker validity and implementation strategies.
Main Results:
- PARP inhibitors have demonstrated significant success in clinical trials for ovarian cancer.
- Germ line BRCA mutations are present in nearly 20% of high-grade serous ovarian cancer cases.
- A substantial proportion of BRCA-mutated patients may not have a prior cancer diagnosis, necessitating broader testing.
Conclusions:
- Widespread implementation of germ line BRCA testing is essential for optimal ovarian cancer patient management.
- PARP inhibitors represent a significant advancement in treating BRCA-mutated ovarian cancer.
- Further research into biomarkers of homologous-recombination deficiency is warranted.
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