PARP Inhibitor Delays Progression of Ovarian Cancer

PARP Inhibitor Delays Progression of Ovarian Cancer

In a phase II clinical trial, olaparib (a type of targeted therapy known as a PARP inhibitor) delayed cancer progression when given after chemotherapy to women with relapsed, platinum-sensitive, serous ovarian cancer. These results will be presented at the 2011 annual meeting of the American Society of Clinical Oncology.

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 22,000 new cases and 14,000 deaths in 2010.

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 investigational targeted 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 have a DNA repair deficiency are thought to be particularly likely to respond to PARP inhibitors, and up to half of high-grade serous ovarian cancers may fall into this category.

To assess the safety and efficacy of olaparib in ovarian cancer, researchers conducted a Phase II clinical trial of 265 women with relapsed, platinum-sensitive, serous ovarian cancer. After treatment with chemotherapy, women were assigned to further treatment (maintenance therapy) with either olaparib or a placebo.

  • Women in the olaparib group remained free of cancer progression longer than women in the placebo group: median progression-free survival was 8.4 months in the olaparib group and 4.8 months in the placebo group.
  • Side effects that were more common in the olaparib group included nausea, fatigue, vomiting, and anemia.

The results of this study suggest that olaparib is active against ovarian cancer. In a prepared statement, the lead author of the study noted A well-tolerated antitumor agent that could be used for months or perhaps years as maintenance therapy after standard chemotherapy could be a big step forward and ultimately extend survival. This study demonstrates proof of principle for the concept of maintenance therapy in ovarian cancer using a PARP inhibitor. Our progression-free survival difference was very impressive and better than we anticipated.

Reference: Ledermann JA, Harter P, Gourley C et al. Phase II randomized placebo-controlled study of olaparib (AZD2281) in patients with platinum-sensitive relapsed serious ovarian cancer (PSR SOC). Paper presented at: 2011 Annual Meeting of the American Society of Clinical Oncology; June 3-7, 2011; Chicago, IL. Abstract 5003.

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