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Stanford University School of Medicine

In international phase-3 clinical trial, new drug shown to prolong ovarian cancer remission

More than 20,000 women are diagnosed with ovarian cancer each year in the United States, most of whom have advanced disease. Although chemotherapy can put the disease into remission, it often recurs and the treatment's effectiveness tends to wane over time. As a result, ovarian cancer is the fifth most-common cause of cancer death in women.

On Saturday, a team of researchers including Stanford oncologist Jonathan Berek, MD, presented the results of an international, multi-center phase-3 clinical trial of a new oral medication called niraparib in 553 women with advanced, recurrent ovarian cancer at the annual meeting of the European Society for Molecular Oncology in Copenhagen. Berek, the Laurie Kraus Lacob Professor and director of the Stanford Women's Cancer Center, supervised Stanford's involvement in the trial.

The aim of the study was to see whether niraparib could prolong the length of remission, also known as "progression-free survival," in the women when compared to treatment with a placebo. As Berek described the niraparib treatment for me in an phone call, "This is a daily oral treatment with relatively low toxicity. Importantly, women don't have to go to the hospital for regular infusions and are unlikely to experience significant hair loss."

Trial participants, who had gone into remission after two or more rounds of platinum-based chemotherapy (usually in the form of the drugs carboplatin and cisplatin along with paclitaxel), were separated into two groups: those who had mutations in the cancer-associated genes BRCA1 and BRCA2, and others who did not have these mutations. BRCA1 and 2 mutations significantly increase the likelihood of developing breast and ovarian cancers. The proteins encoded by the BRCA genes are involved in a process of DNA repair called homologous recombination. Niraparib belongs to a class of medications called PARP inhibitors that also hamper a cell's ability to repair DNA damage; these medications have been shown in other trials to be particularly effective in promoting death in cells with BRCA mutations.

Two-thirds of the women in each group were assigned to receive niraparib once a day and the remaining one-third in each group received a placebo. The researchers found that those women who were taking niraparib experienced significantly longer progression-free survival than those who had been taking a placebo -- a median of 21 months versus 5.5 months for the BRCA mutations group and a median of 9.3 months versus 3.9 for the group without BRCA mutations. When the researchers further subdivided the non-BRCA mutations group into those with other known problems in homologous recombination and those without, they still saw a benefit of the drug. In particular, those women with mutations known to affect homologous recombination who received niraparib experienced a median progression-free survival of 12.9 months versus 3.8 months for those who had been taking the placebo.

As Berek, who helped design the trial, explained:

The results are striking. The treatment gave a statistically significant benefit for all the groups. It worked best for those women who had a mutation in one of the BRCA proteins. But it also worked in women who didn't have known mutations, just not as well. This drug, if it is approved by the Food and Drug Administration, will likely lead to a paradigm shift in how I and my colleagues around the world treat women with ovarian cancers.

The company that makes the drug, Massachusetts-based Tesaro, Inc, provided funding for the clinical trial and has provided Berek with research funding. In early September the Food and Drug Administration granted Fast Track designation to niraparib to speed its review of the drug and, if appropriate, hasten its approval for routine clinical use.

The researchers published the results of the trial online in the New England Journal of Medicine this weekend to coincide with the meeting's presentation.

Previously: Networking to save lives: A Q&A on ovarian cancer, Study shows daily aspirin could lower women's risk of ovarian cancer and Frontiers in the fight against ovarian cancer
Photo of Jonathan Berek courtesy of Stanford Cancer Center

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