In the last decade treatment of ovarian cancer has shifted from a ‘one size fits all’
approach to biologically determined treatment options. This has been driven by an
understanding of the importance of BRCA mutations to predict the benefit of PARP inhibitor treatment. Mutations in the BRCA gene, whether germline or somatic are found in about 20–25% of women with high grade
ovarian cancers. During the early PARP inhibitor studies with olaparib, it became
clear that non-BRCA-related mechanisms may also be responsible for defects in the DNA homologous recombination
repair pathway which are key to successful PARP inhibitor activity. An improvement
in progression-free survival (PFS) after a recurrence was also seen in women with
BRCA wild-type tumours when maintenance therapy with PARP inhibitors was used following a response
to platinum-based therapy [
[1]
]. The hallmark of activity is HR deficiency (HRD) and is present in approximately
50% patients with high grade serous cancers [
[2]
]. However, in recurrent ovarian cancer HRD has been a less useful discriminant of
PARP inhibitor benefit than a response to platinum-based therapy [
[3]
,
[4]
]. Consequently, PARP inhibitors are licensed for maintenance treatment in recurrent
ovarian cancer after a response to platinum-based therapy, irrespective of BRCA status
[
[5]
]. Ovarian cancer research has now shifted to explore PARP inhibitor maintenance therapy
in the first-line setting.To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Gynecologic OncologyAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Olaparib maintenance therapy in platinum-sensitive relapsed ovarian cancer.N. Engl. J. Med. 2012; 366: 1382-1392
- Homologous recombination deficiency: exploiting the fundamental vulnerability of ovarian cancer.Cancer Discov. 2015; 5: 1137-1154
- Rucaparib maintenance treatment for recurrent ovarian carcinoma after response to platinum therapy (ARIEL3): a randomised, double-blind, placebo-controlled, phase 3 trial.Lancet. 2017; 390: 1949-1961
- Niraparib maintenance therapy in platinum-sensitive, recurrent ovarian cancer.N. Engl. J. Med. 2016; 375: 2154-2164
- Latest clinical evidence and further development of PARP inhibitors in ovarian cancer.Ann. Oncol. 2018; 29: 1366-1376
- Maintenance olaparib in patients with newly diagnosed advanced ovarian cancer.N. Engl. J. Med. 2018; 379: 2495-2505
- Veliparib with first-line chemotherapy and as maintenance therapy in ovarian cancer.N. Engl. J. Med. 2019; 381: 2403-2415
- Niraparib in patients with newly diagnosed advanced ovarian cancer.N. Engl. J. Med. 2019; 381: 2391-2402
- Olaparib plus bevacizumab as first-line maintenance in ovarian cancer.N. Engl. J. Med. 2019; 381: 2416-2428
- Weekly dose-dense chemotherapy in first-line epithelial ovarian, fallopian tube, or primary peritoneal carcinoma treatment (ICON8): primary progression free survival analysis results from a GCIG phase 3 randomised controlled trial.Lancet. 2019; 394: 2084-2095
- Impact of homologous recombination status and responses with veliparib combined with first-line chemotherapy in ovarian cancer in the Phase 3 VELIA/GOG-3005 study.Gynecol Oncol. 2021; 164: 245-253
- Incorporation of bevacizumab in the primary treatment of ovarian cancer.N. Engl. J. Med. 2011; 365: 2473-2483
- Homologous Recombination Deficiency Assays in Epithelial Ovarian Cancer: Current Status and Future Direction.Front. Oncol. 2021; 11
Article info
Identification
Copyright
© 2022 Elsevier Inc. All rights reserved.
