Olaparib Shows Promise in High-grade Serous Ovarian Cancer

Posted on June 16th, 2010 by

Advanced serous ovarian cancer responds to single-agent treatment with olaparib, according to the results of a Phase II study presented at the 2010 annual meeting of the American Society of Clinical Oncology.[1]

Ovarian cancer has the highest mortality rate of all gynecologic cancers. It is the fifth leading cause of cancer death among U.S. women, with an estimated 21,550 new cases and 14,600 deaths in 2009.

Treatment for ovarian cancer commonly involves surgery and/or chemotherapy. Outcomes for women diagnosed with advanced disease remain poor, and researchers continue to evaluate new approaches to treatment.

Targeted therapies are anticancer drugs that interfere with specific pathways involved in cancer cell growth or survival. Some targeted therapies block growth signals from reaching cancer cells; others reduce the blood supply to cancer cells; and still others stimulate the immune system to recognize and attack the cancer cell. Depending on the specific “target,” targeted therapies may slow cancer cell growth or increase cancer cell death.

Olaparib is an oral investigational drug called a PARP inhibitor. The PARP enzyme plays a role in DNA repair, including the repair of DNA damage from chemotherapy. Drugs that inhibit this enzyme may contribute to cancer cell death and increased sensitivity to chemotherapy. Cancers that result from BRCA1 or BRCA2 gene mutations (such as ovarian cancer) may be particularly responsive to PARP inhibitors. Olaparib has previously been shown to have activity in advanced ovarian and breast cancers with BRCA mutations.

A Phase II study evaluated the use of olaparib as a single agent in the treatment of advanced serous ovarian cancer and triple-negative breast cancer. The study involved 64 women with advanced ovarian cancer and 24 with triple-negative advanced breast cancer.

The results indicated that 41.2% of women with ovarian cancer and BRCA mutations achieved objective responses with single-agent olaparib. Furthermore, the objective response rate among women with ovarian cancer, but without BRCA mutations, was 23.9%. There was no response observed among the 24 women with triple-negative advanced breast cancer treated with orlapinib.

These are the first data indicating promising activity from single-agent orlapinib in high-grade non-BRCA serous ovarian cancer. The researchers speculated that this may indicate that serous ovarian cancer could be a disease of impaired DNA repair. More research is necessary, but these are promising preliminary results for orlapinib.

Reference:


[1] Gelmon KA, Hirte HW, Robidoux A, et al. Can we define tumors that will respond to PARP inhibitors? A phase II correlative study of olaparib in advanced serous ovarian cancer and triple-negative breast cancer. Presented at the 2010 annual meeting of the American Society of Clinical Oncology. June 4-8, 2010. Chicago, IL. Abstract 3002.

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