New breast cancer drugs block cell repair enzyme

ORLANDO, Florida Sun May 31, 2009 3:41pm EDT

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ORLANDO, Florida (Reuters) - Drugs that block a cell repair enzyme known as PARP show promise as treatments for some of the most aggressive and difficult-to-treat forms of breast cancer, according to new research.

Mid-stage results from a PARP inhibitor developed by BiPar Sciences Inc show that it improved survival by 60 percent compared with chemotherapy alone for women with "triple negative breast cancer."

And a small trial of AstraZeneca Plc's olaparib as a stand-alone therapy in women with advanced breast cancer linked to genetic mutations showed that it shrank tumors in a third of patients.

"While still very preliminary, these are some of the most exciting results we have seen in a long time," said Dr. Eric Winer, breast cancer chief at Boston's Dana-Farber Cancer Center.

The findings were presented on Sunday at the annual meeting of the American Society of Clinical Oncology.

PARP is short for "poly (ADP-ribose) polymerase," which is used by cancer cells to repair DNA damage, including the damage inflicted by chemotherapy drugs. By blocking the enzyme, researchers aim to further undermine the ability of cancer cells to heal themselves.

Breast cancer was one of first types of cancer that scientists have been able to divide into subgroups based on biological markers.

Back in the 1970s they identified women whose tumors contained estrogen receptors -- paving the way for the development of hormonal therapies, like tamoxifen and aromatase inhibitors.

That breakthrough was followed by the launch in 1998 of Herceptin, an antibody-based drug designed to target the HER-2 protein, which is generated by around 25 percent of breast cancer patients.

NEXT BREAST CANCER BREAKTHROUGH

"The third breakthrough is this one," said Dr. Barry Sherman, head of development at BiPar, which presented results from a 116-patient trial of its intravenous PARP inhibitor, known as BSI-201.

Privately held BiPar agreed in April to be purchased by French drugmaker Sanofi Aventis SA for up to $500 million.

BSI-201 is being studied in women with "triple negative" metastatic breast cancer, meaning their tumors do not express the hormones estrogen or progesterone as well as HER-2.

These women, accounting for 15 to 20 percent of breast cancer patients, have a very aggressive form of the disease and there are currently no treatments beyond chemotherapy, Sherman said.

The BiPar trial found women who received BSI-201 had a median survival of 9.2 months, compared with 5.7 months for the chemotherapy-only group. Tumors shrank in nearly half of patients treated with the BiPar drug, compared with just 16 percent of patients on chemotherapy alone.

Side effects were similar for both groups.

Sherman said the company expects to launch a larger pivotal-stage trial of BSI-201 this summer.

Anglo-Swedish AstraZeneca presented data from a 57-patient trial of its oral PARP inhibitor, olaparib, in heavily pre-treated patients with advanced cancer carrying the BRCA1 or BRCA2 gene mutation.

The trial found that more than a third of patients experienced tumor shrinkage after treatment with the higher of two doses of olaparib.

"Some of these responses were extremely durable and a number of patients continue on treatment beyond one year of therapy," said James Carmichael, medical science director of AstraZeneca's olaparib program.

Fatigue, nausea and vomiting were the most common side effects.

AstraZeneca is looking to expand its study of olaparib to include patient populations broader than BRCA mutation carriers, said Geert Kolvenbag, the company's global product vice president, oncology. He also said there are a number of ongoing trials of the drug in combination with common chemotherapy agents.

Carmichael said there is good evidence that a significant portion of patients with other types of cancer have genetic mutations that would make them candidates for treatment with a PARP inhibitor. "We are looking at how frequent they are and how to identify them," he said.

The BRCA deficient population represents about 5 percent of overall breast cancer patients, and many of them are also "triple negative," Carmichael said.

A prior Phase II study showed that some women with BRCA-deficient ovarian cancers responded to olaparib.

(Reporting by Deena Beasley, editing by Matthew Lewis and Tim Dobbyn)

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