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by Lisa Rezende, PhD
Use of rucaparib in advanced ovarian cancer: Results from the ARIEL 2 trial
The PARP inhibitor olaparib has been approved for ovarian cancer patients with inherited mutations in BRCA1 or BRCA2. Some studies have shown that PARP inhibitors could also be effective in treating ovarian cancers in certain women who have not inherited mutations in one of these genes. If researchers could identify the characteristics of tumors that respond to PARP inhibitors, they could develop ways of finding women whose cancers can be successfully treated with these agents. Dr. Iain McNeish presented results from the ARIEL 2 trial that studied the use of the PARP inhibitor rucaparib in women with recurrent ovarian cancer. Researchers looked at tumor cells characteristics called “genome scarring” to see if these tumors could be treated with PARP inhibitors.
In this study, 204 women who had high-grade serous ovarian cancer and had relapsed after taking a platinum drug were given rucaparib. Tumors from these women were analyzed for BRCA mutations and genomic scarring and were categorized into one of three groups:
Rucaparib was most effective in treating tumors from women with BRCA mutations, having an overall response rate of over 80%. BRCA-like tumors also responded to rucaparib. The drug was well tolerated; nausea and fatigue were the most commonly reported side effects. The ARIEL 2 trial is ongoing. Please see our featured studies page for more information.
Other PARP inhibitor news
A session at the 2015 ASCO national meeting was devoted to discussing the proposal by Dr. Mary-Claire King to offer screening for BRCA mutations to all women at age 30.
Dr. Elizabeth Swisher presented arguments for universal testing. Noting that inexpensive and accurate testing is now available, the current testing criteria based on family history would miss about one-third of mutation carriers even if all eligible women were referred for testing. Dr. Swisher outlined how BRCA testing fits the criteria for a broad screening program, including:
Dr. Swisher noted that when genetic testing is based on family history alone, many women are missed because they come from small families or families with a mutation that is inherited from the father’s side. Studies have shown that physicians do not always record or recognize family cancer history, and in some cases women who meet current guidelines for genetic counseling and testing are not referred. Dr. Swisher closed with a quote from Dr. Mary-Claire King: “Every breast or ovarian cancer patient with a BRCA1 or BRCA2 mutation detected after diagnosis is a missed opportunity to prevent cancer.”
Dr. Mark Robson discussed arguments against universal testing for BRCA mutations. He noted that no population-based genetic screening programs for adult-onset disorders exist—universal BRCA testing would be the first. He presented the potential benefits and harms of universal screening from a public health prospective. He noted that only a fraction of all breast and ovarian cancers are associated with inherited BRCA mutations, therefore universal screening will have only minimal impact on the entire population. The majority of women will receive a negative test result, which will not change their health care management. Women with a negative result will have to be counseled appropriately to be sure they understand their risk of breast cancer, particular if they have a family history, but no mutation in BRCA1 or BRCA2.
Dr. Robson also outlined potential harms associated with the frequency of false positive tests, the possibility of over diagnosis, and harms from treatments. He noted that no test is 100% accurate. Based on recent studies of genetic testing accuracy, approximately 1 in 1,000 women will receive a false positive, meaning they will be told they have a mutation in BRCA1 or BRCA2 when they do not. Second, Dr. Robson noted that not all women who have a BRCA mutation will develop cancer. Because many factors influence overall lifetime cancer risk in BRCA mutation carriers it is unclear how many women identified by population-based BRCA screening would eventually develop cancer. Dr. Robson agrees we need to do a better job of identifying BRCA mutation carriers before they develop cancer. He proposed a number of alternatives including:
Both speakers and audience members who asked questions after the presentation agreed that we must do a better job finding BRCA mutation carriers before they develop cancer.
posted August 29, 2015