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

Cochrane Review shows new medication used to treat women with advanced ovarian cancer delays need for further treatment in some women.

Cochrane Review shows new medication used to treat women with advanced ovarian cancer delays need for further treatment in some women

Ovarian cancer is the sixth most common cancer in women world-wide. Treatment of ovarian cancer consists of a combination of surgery and chemotherapy.  Conventional chemotherapy drugs act on dividing cells by damaging cell DNA. As cancer cells divide very rapidly, these drugs affect cancer cells to a greater degree than normal cells. Being able to repair DNA is vital to cell survival and normal cells have more than one DNA repair pathway. However, cancer cells often have defects in these repair pathways that make them more susceptible to DNA damage. PARP inhibitors are a new type of medication that works by preventing cancer cells from repairing their DNA once they have been damaged by chemotherapy.

A team of Cochrane authors based in the United Kingdom worked with the  Cochrane Gynaecological Cancer Group to determine to determine the benefits and risks of PARP inhibitors for the treatment of epithelial ovarian cancer.

This review assesses four RCTs involving 599 women with the most common form of advanced ovarian cancer who received treatment with the new drug. Three trials included women who had ‘platinum-sensitive’ disease (which means a return of disease more than 12 months since last chemotherapy treatment), and one included women with platinum-resistant and partially platinum-sensitive disease (return of disease less than six months or six to 12 months since last chemotherapy treatment). The authors also identified four ongoing studies. On average, when added to conventional treatment, olaparib given as maintenance treatment following chemotherapy increased the time before further chemotherapy was required by 3-4 months, compared with placebo or no added treatment, for women with platinum-sensitive disease.  There were too few women in the studies to determine whether there was any improvement in how long women survived overall. PARP-inhibitors seem to be more effective in women who carry the BRCA-mutation (a genetic predisposition to ovarian and breast cancer), although numbers were small and researchers await results of further ongoing studies.  Adverse events were common in both the PARP inhibitor group and the control group. However, serious adverse events were more common in the olaparib group than the control group when given as maintenance treatment after a course of chemotherapy. The most common serious adverse events were anaemia and fatigue. Veliparib had few severe side effects, but the numbers were too small for meaningful conclusions.

This new research included previously unpublished data; Astra Zeneca provided these to the Cochrane authors prior to their publication, which occurred while the Cochrane Review peer review process was under way.  Researchers also await the results of a NICE Health Technology Appraisal which will examine the cost effectiveness of treatment, as well as considering clinical effectiveness.

“PARP inhibitors may improve the time without tumor progression in some women with recurrent platinum-sensitive disease by 3-4 months. Ongoing studies are likely to provide more information about PARP-inhibitors and their role in overall survival rates for women with advanced ovarian cancer,” said Alison J Wiggans, a researcher at Musgrove Park Hospital in Somerset, UK and joint lead author of the Cochrane Review. “Astra Zeneca were extremely helpful in releasing previously unpublished data. It’s important that future reviews, both in oncology and in other fields, look not just published results in academic journals, but also look for unpublished data and ongoing trials to get an accurate overview.”

Read the full Cochrane Review

WHO position statement on public disclosure of clinical trial data

Monday, July 20, 2015