Poly(ADP-ribose) polymerase (PARP) inhibitors for the treatment of ovarian cancer

69Citations
Citations of this article
213Readers
Mendeley users who have this article in their library.

This article is free to access.

Abstract

Background: Ovarian cancer is the sixth most common cancer and seventh most common cause of cancer death in women world-wide. Three-quarters of women present when the disease has spread throughout the abdomen (stage III or IV) and treatment consists of a combination of debulking surgery and platinum-based chemotherapy. Although initial responses to chemotherapy are good, most women will relapse and require further chemotherapy and will eventually develop resistance to chemotherapy. PARP (poly (ADP-ribose) polymerase) inhibitors, are a novel type of medication that works by preventing cancer cells from repairing their DNA once they have been damaged by other chemotherapy agents. It is not clear how PARP inhibitors compare to conventional chemotherapy regimens for the treatment of ovarian cancer, with respect to survival, side effects and quality of life. Objectives: To determine the benefits and risks of PARP inhibitors for the treatment of epithelial ovarian cancer (EOC). Search methods: We identified randomised controlled trials (RCTs) by searching the Cochrane Central Register of Controlled Trials (CENTRAL 2015, Issue 3), the Cochrane Gynaecological Cancer Group Trial Register, MEDLINE (1990 to April 2015), EMBASE (1990 to April 2015), ongoing trials on www.controlled-trials.com/rct, www.clinicaltrials.gov, www.cancer.gov/clinicaltrials and the National Research Register (NRR), the FDA database and pharmaceutical industry biomedical literature. Selection criteria: Women with histologically proven EOC who were randomised to treatment groups in trials that either compared PARP inhibitors with no treatment, or PARP inhibitors versus conventional chemotherapy, or PARP inhibitors together with conventional chemotherapy versus conventional chemotherapy alone. Data collection and analysis: We used standard Cochrane methodology. Two review authors independently assessed whether studies met the inclusion criteria. We contacted investigators for additional data, where possible. Outcomes included survival, quality of life and toxicity. Main results: We included four RCTs involving 599 women with EOC. Data for veliparib were limited and of low quality, due to small numbers (75 women total). Olaparib, on average, improved progression-free survival (PFS) when added to conventional treatment and when used as maintenance treatment in women with platinum-sensitive disease compared with placebo (hazard ratio (HR) 0.42, 95% confidence interval (CI) 0.29 to 0.60; 426 participants; two studies), but did not improve overall survival (OS) (HR 1.05, 95% CI 0.79 to 1.39; 426 participants; two studies). We graded this evidence as moderate quality using the GRADE approach. Adverse events of any severity were common in both the PARP inhibitor group and the control group. Olaparib was associated with more severe adverse events (G3/4) during the maintenance phase compared with controls (risk ratio (RR) 1.74, 95% CI 1.22 to 2.49; 385 participants, two studies; high quality evidence). Quality of life data were insufficient for meta-analysis. We identified four ongoing studies. Authors' conclusions: PARP inhibitors appear to improve PFS in women with recurrent platinum-sensitive disease. Ongoing studies are likely to provide more information about whether the improvement in PFS leads to any change in OS in this subgroup of women with EOC. More research is needed to determine whether PARP inhibitors have any role to play in platinum-resistant disease.

Cite

CITATION STYLE

APA

Wiggans, A. J., Cass, G. K. S., Bryant, A., Lawrie, T. A., & Morrison, J. (2015, May 20). Poly(ADP-ribose) polymerase (PARP) inhibitors for the treatment of ovarian cancer. Cochrane Database of Systematic Reviews. John Wiley and Sons Ltd. https://doi.org/10.1002/14651858.CD007929.pub3

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free