The treatment landscape in the coming decade for ovarian cancers will likely feature poly ADP ribose polymerase (PARP) inhibitors in combination with other treatments, according to reports from a recent conference.
Many types of drugs have been approved for the treatment of ovarian cancer since the 1990s, including platinum-based chemotherapies, taxane chemotherapies, and anti-angiogenesis drugs. Since 2014, the first PARP inhibitor was approved and such inhibitors have since ballooned into the most commonly approved drug type for BRCA-positive ovarian cancer.
According to Elise C Kohn, MD, head of gynecologic cancer therapeutics, Cancer Therapy Evaluation Program, National Cancer Institute, at a presentation during the 10th Annual Conference of Facing Our Risk of Cancer Empowered (June 10, 2017; Orlando, FL), PARP inhibitors work particularly well with chemotherapies; cytotoxic drugs damage tumor DNA and PARP inhibitors prevent the DNA from repairing itself. Dr Kohn cited two studies that showed using chemotherapy followed by a PARP inhibitor to help maintain responses improves survival outcomes.
However, these studies have also confirmed that PARP inhibitors are not effective in all patients with ovarian cancers. Researchers have since begun to explore whether combining PARP inhibitors with other drugs might result in improved efficacy. Dr Kohn and colleagues studied carboplatin in combination with a PARP inhibitor and found that “women with germline mutations responded phenomenally and longer.”
Additional strategies are being examined as potential therapies for ovarian cancers as well, according to Dr Kohn. In a phase II/III study, Dr Kohn and researchers are monitoring the responses of women with platinum-resistant ovarian cancers (some of whom exhibit BRCA-positive disease) after administering single-agent chemotherapy versus a PARP inhibitor, cediranib, or a combination of the two.
Dr Kohn noted that the immune system generally does not detect cancers caused by germline mutations. Adding abnormalities to cancer cells with chemotherapy and PARP inhibitors may induce better cancer detection. As a result, combination of immunotherapy drugs with a PARP inhibitor or cediranib may prove to be significantly efficacious, she said.—Zachary Bessette