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

• Published in: Cochrane database of systematic reviews 2015-05, Vol.2015 (5), p.CD007929
• Main Authors: Wiggans, Alison J, Cass, Gemma K S, Bryant, Andrew, Lawrie, Theresa A, Morrison, Jo
• Format: Article
• Language: English
• Subjects: Adult; Antineoplastic Agents - therapeutic use; Benzimidazoles - adverse effects; Benzimidazoles - therapeutic use; Disease-Free Survival; DNA Repair - drug effects; Female; Humans; Medicine General & Introductory Medical Sciences; Neoplasm Recurrence, Local - drug therapy; Ovarian Neoplasms - drug therapy; Ovarian Neoplasms - genetics; Phthalazines - adverse effects; Phthalazines - therapeutic use; Piperazines - adverse effects; Piperazines - therapeutic use; Poly(ADP-ribose) Polymerase Inhibitors; Randomized Controlled Trials as Topic
• ISSN: 1469-493X; 1469-493X
• DOI: 10.1002/14651858.CD007929.pub3

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. To determine the benefits and risks of PARP inhibitors for the treatment of epithelial ovarian cancer (EOC). We identified randomised controlled trials (RCTs) by searching the Cochrane Central Register of Controlled Trials (CENTRAL 2014, Issue 4), the Cochrane Gynaecological Cancer Group Trial Register, MEDLINE (1990 to May 2014), EMBASE (1990 to May 2014), 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. 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. 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. 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 participa