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Olaparib Prompts Interest as Potential Treatment for Hereditary-Based Breast Cancers

October 9, 2009

Written By Christine Cardellino
Reviewed By Susan M. Domchek, MD

A phase II clinical trial of olaparib (AZD-2281) showed that the medicine benefited women whose metastatic breast cancer was caused by defects in the BRCA1 or BRCA2 gene and had grown despite previous treatment with chemotherapy.

The study, presented during the 2009 annual meeting of the American Society of Clinical Oncology , looked at a new type of targeted therapy known as poly ADP-ribose polymerase (PARP) inhibitors. These new medicines are believed to affect an enzyme that repairs DNA damage in cells when used to treat breast cancer alone or in combination with chemotherapy (combination therapy).

Although this was a small, early study of the safety and effectiveness of olaparib, the lead investigator called the results "very promising" for the treatment of hereditary breast cancers. Researchers will continue to study olaparib in new clinical trials.

About PARP Inhibitors

Chemotherapy is the one of the standard treatments for cancers caused by defects in the BRCA1 or BRCA2 gene. But chemotherapy kills all fast-growing cells, not just cancer cells. Researchers are searching for new, targeted medicines that would attack only the cells involved in BRCA-specific breast cancers.

The new type of targeted therapy involved in this clinical trial, a PARP inhibitor , blocks enzymes in the cancer cells that help them repair their damaged DNA. When cancer cells cannot repair their DNA after treatment, the cells eventually die or get smaller.

The medicine involved in this clinical trial, olaparib, is a pill that is taken by mouth. A phase I trial, published in late June 2009 in the New England Journal of Medicine, inspired this phase II study of olaparib and other ongoing research into the effectiveness of the medicine in people with BRCA mutations. The earlier study compared the effectiveness of olaparib in people with BRCA mutations to those without them. Results showed only participants with the mutations benefited from the PARP inhibitor. To learn more about this study, read the abstract .

Study Design

Women with advanced, BRCA-related breast cancer took part in this study. All the women had previously been treated with several regimens of chemotherapy.

Of the 54 participants, 27 received 100 milligram (mg) doses of olaparib twice daily, and 27 received a 400 mg dose twice a day. The study design did not include a control group, a group of participants who did not receive the study medicine for comparison.

Study Results

This was the first-ever clinical trial of olaparib that focused on BRCA-deficient breast cancer. Forty percent of women receiving the 400 mg dose saw their tumors get smaller or slow in growth. Olaparib had a smaller, but still significant, benefit in 22 percent of the women who received the 100 mg dose.

In most participants, side effects of treatment with olaparib included fatigue, nausea, and vomiting. These were considered mild and controllable.

What Does This Study Mean for Me?

PARP inhibitors such as olaparib have the potential to be a breakthrough treatment for hereditary breast cancers, and research in this emerging field continues. Although medical researchers are excited about these promising early study results, PARP inhibitors must be taken by more women in clinical trials before the treatment can become a standard of care.

If you have been diagnosed with a BRCA-related metastatic breast cancer, you and your doctor may discuss a variety of treatment options, including chemotherapy or targeted therapies. When considering these options, ask your doctor about the risks and benefits of participating in a clinical trial of new treatments such as PARP inhibitors.

If breast cancer runs in your family, you may wish to ask your doctor about genetic testing for you and your loved ones. Learning that you have an increased risk for developing cancer can enable you to take steps to lower that risk.

You also may wish to read our helpful publication, Understanding Treatment Options for Advanced Breast Cancer, which you can order or download for free at our Marketplace .

  1. Tutt et al. Phase II trial of the oral PARP inhibitor olaparib in BRCA-deficient advanced breast cancer. Presented at the 2009 Annual Meeting of the American Society of Clinical Oncology (ASCO). Abstract CRA501.

Read the abstract on olaparib in BRCA-deficient metastatic breast cancer.