PARP inhibitors in platinum-sensitive high-grade serous ovarian cancer

Cancer Chemother Pharmacol. 2018 Apr;81(4):647-658. doi: 10.1007/s00280-018-3532-9. Epub 2018 Feb 20.


Purpose: Poly(ADP-ribose) polymerase inhibitors (PARPi) have changed the management of high-grade serous ovarian cancer (HGSOC). The rationale for the development of PARPi was based on the concept of synthetic lethality, in which a cell can survive a deficiency of one gene/gene product, but may die if there is a deficiency in a combination of genes/gene products. In women with BRCA1/2 deficiency within their ovarian cancer tissue, inhibition of PARP imposes an intolerable burden of DNA damage repair deficiency and may induce cell death.

Methods: Clinical trials have evaluated PARPi as single-agent therapeutics and as maintenance treatment following platinum-based chemotherapy for HGSOC. Clinical data suggest the most impressive anti-tumour activity occurs in women with platinum-sensitive ovarian cancer and germline or somatic BRCA1/2 mutations (g/sBRCAmt).

Results: In the maintenance setting, randomised trials have shown that PARPi compared to placebo reduce the hazard ratio for the development of progressive disease to 0.2-0.27 for patients with a g/sBRCAmt; to 0.34-0.38 for patients with putative evidence of DNA damage repair deficiency; and to 0.35-0.45 in an unselected population with HGSOC. Furthermore, phase 1/2 trials have reported single-agent anti-tumour response rates in gBRCAmt of approximately 50% in platinum-sensitive and 25% in platinum-resistant disease.

Conclusion: Here, we discuss the evidence for the use of PARPi as single-agent therapeutics and maintenance treatment in HGSOC and evaluate the genetic assays used in clinical trials so far. We discuss the emerging role of platinum sensitivity as a broad eligibility criteria for the use of PARPi.

Keywords: BRCA mutation; Ovarian cancer; PARP inhibitors; Platinum sensitivity.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Cystadenocarcinoma, Serous / drug therapy*
  • Cystadenocarcinoma, Serous / metabolism
  • Drug Resistance, Neoplasm / drug effects*
  • Female
  • Humans
  • Ovarian Neoplasms / drug therapy*
  • Ovarian Neoplasms / metabolism
  • Platinum / administration & dosage*
  • Poly(ADP-ribose) Polymerase Inhibitors / therapeutic use*


  • Poly(ADP-ribose) Polymerase Inhibitors
  • Platinum