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Drug combos could hold off advanced breast cancer, studies say

Combinations of drugs could impede advanced breast cancer tumors in different ways, two large studies suggest.

December 07, 2011|By Shari Roan, Los Angeles Times
  • A woman with advanced breast cancer receives medication.
A woman with advanced breast cancer receives medication. (Francine Orr / Los Angeles…)

Treatment for advanced breast cancer could improve significantly if doctors give women combinations of medications that attack tumors in different ways, two large clinical trials suggest.

In one study, researchers found patients fared better when a breast cancer drug called an aromatase inhibitor was combined with another medication, Afinitor, which is used to treat kidney cancer but is not yet approved for breast cancer. In the second study, two standard medications for women with a type of breast cancer known as HER2-positive were more effective when the investigational drug pertuzumab was added to the regimen.

The findings, reported Wednesday at the annual San Antonio Breast Cancer Symposium, point to a new paradigm in treating advanced breast cancer, a field that has not seen significant progress in recent years, cancer specialists said. The studies signal that advanced breast cancer may be best treated with a strategic combination of targeted medications that wage war on the cancer along several biological pathways.

"These are two terrific, new options. They are laying out a map on the way forward for breast cancer," said Dr. José Baselga, a professor of medication at Harvard Medical School who was involved in both trials. "The way forward is by doing smart combination therapies."

The approach in many ways mimics that used in treating those who are infected by HIV: Just as treatment with multiple drugs cuts the chance that the virus can develop resistance, attacking the cancer cells on multiple fronts reduces the chance that the tumors can mutate to thwart the assault against them.

Scientists cautioned that the data so far show only that the patients survived longer before their tumor advanced in size. They have not shown that survival rates are lengthened as well.

But the two large trials are relevant to the lion's share of cases of advanced breast cancer as well as some of the most dangerous ones, Baselga said. About 60% of all cases of advanced breast cancer are of the hormone receptor-positive type, and HER-2 positive cases are among the more aggressive cancer.

Neither of the regimens in the studies represent a cure, but they could buy more time for patients who are running out of options, oncologists said.

The first study, known by the acronym BOLERO-2, included 724 postmenopausal patients who had received standard therapies but whose cancers had spread to other organs.

All of the patients had hormone receptor-positive breast cancers, which are treated with aromatase inhibitors to block the supply of estrogen their cancer cells need to grow. But the cancers often develop resistance to the aromatase inhibitors and can grow even without an estrogen supply. Afinitor blocks the cancer cells at a different biological point, preventing this estrogen-free growth.

In the study, patients receiving the aromatase inhibitor exemestane plus Afinitor had an average of 7.4 months of time during which their cancers did not grow compared with 3.2 months for the women receiving exemestane and a placebo.

"This dual blockage is a more complete blockage," said study coauthor Dr. Gabriel Hortobagyi, chairman of the department of breast medical oncology at the University of Texas M.D. Anderson Cancer Center in Houston. "This is the first time we've achieved this."

The study reflects continued progress against the disease, said Dr. Sara Hurvitz, director of the breast oncology program at the UCLA Jonsson Comprehensive Cancer Center, who was not involved in the study.

"This is important because we haven't seen a lot of dents in our ability to treat hormone-positive disease in the past five or 10 years," she said.

Women in the second trial, known as CLEOPATRA, had advanced cases of a type of breast cancer in which extra copies of a protein called HER2 stud the surface of cancer cells. This produces an aggressive tumor. Herceptin was designed specifically to treat HER2-positive breast cancer, but women with advanced disease often become resistant to it.

The 808 patients, who were newly diagnosed with advanced disease and had not received prior medications, were randomized to receive Herceptin and the chemotherapy drug docetaxel or those two medications plus pertuzumab.

Patients receiving pertuzumab experienced 18.5 months free of cancer growth, compared with 12.4 months for those who received a placebo.

"Herceptin helped a lot of people, but it was not a perfect blocker," Baselga said. "Pertuzumab binds to HER2 the same as Herceptin, but it binds on one site and pertuzumab on the other."

Important caveats surround both studies, which were published online in the New England Journal of Medicine: Researchers can't yet say whether women live longer on the new combination therapies, just that it takes longer for their tumors to start regrowing.

Only last month, the Food and Drug Administration rescinded approval for another drug, Avastin, for advanced breast cancer because although early studies showed it led to longer disease-free periods it did not increase survival.

Baselga said BOLERO-2 and CLEOPATRA were more rigorous clinical trials. But, he added, "the Avastin story has been a great warning to the whole field."

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