AstraZeneca Ovarian Cancer Drug Shows Promise for Aggressive Disease

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The results of the second Phase II study involving AstraZeneca’s olaparib have been released, and the news is promising that the drug is a new treatment option for patients with a more common form of aggressive ovarian cancer.

Olaparib belongs to a class of drugs known as PARP inhibitors. Poly (ADP ribose) polymerase is an enzyme involved in DNA repair. Olaparib blocks the activity of this protein, which prevents cancer cells from repairing themselves, causing them to die.

Karen Gelmon with the BC Cancer Agency in Vancouver, Canada and a team of researchers studied olaparib in 92 patients – 5 with ovarian cancer and 26 with breast cancer. Patients were classified according to their BRCA1 and BRCA2 mutation status. Each received 400 mg twice daily for a 4-week duration between July 2008 and September 2009.

Just over 40% of women with ovarian cancer and BRCA mutations showed a substantial shrinkage in the size of their tumors compared with 24% of patients without the mutation. Unfortunately, none of the patients with breast cancer showed an objective response. Tolerance of the drug was good, with most side effects such as fatigue, nausea, and decreased appetite being mild.

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Gelmon writes in the Lancet Oncology, “To our knowledge, this is the first study to show that olaparib monotherapy has activity in women with pretreated high-grade serous ovarian cancer without germline BRCA1 or BRCA2 mutations. Olaparib represents a promising therapeutic option for patients with this aggressive malignant disease for whom treatment options are limited to toxic chemotherapies."

Over the course of several studies, olaparib has had both positive and negative outcomes. Data presented this year at the American Society of Clinical Oncology found that women with relapsed, platinum-sensitive ovarian cancer responded well to the drug. However, there was no significant effect on progression-free survival among women with advanced BRCA-mutated ovarian cancer.

For more on olaparib, please read:
Phase II Ovarian Cancer Drug Extends Progression-Free Survival
New Drug Reduces Hereditary Ovarian, Breast Cancers

Source references:
Gelmon KA, et al "Olaparib in patients with recurrent high-grade serous or poorly differentiated ovarian carcinoma or triple-negative breast cancer: A phase II, multicenter, open-label, nonrandomized study" Lancet Oncol 2011; 12: 852-861

Telli ML "PARP inhibitors in cancer: Moving beyond BRCA" Lancet Oncol 2011; 12: 827-828.

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