Drug Combo Might Fight Aggressive Breast Cancer More Safely
Posted Oct 05 2011 1:00pm
Study suggests anthracyclines not needed to treat HER2-positive breast cancer, can pose heart risks.
By Kathleen Doheny HealthDay Reporter
WEDNESDAY, Oct. 5 (HealthDay News) -- Treating women with an aggressive form of early stage
breast cancer using Herceptin and chemotherapy, while not turning to a third type of drug known as an anthracycline, improves survival while posing less danger to the heart, researchers report.
They tested three different regimens, one of which did not include any anthracyclines. When Herceptin is given with doxorubicin (Adriamycin), an anthracycline, toxic cardiac effects have been seen.
"What the study shows is you have comparable effectiveness in a Herceptin-based regimen when you don't use the anthracyclines," said Dr. Dennis Slamon, director of clinical and translational research at the Jonsson Comprehensive Cancer Center at the University of California, Los Angeles. Earlier research of his led to the development of Herceptin (trastuzumab).
He contends that the new regimen should be the new standard of care, but one expert who wrote an accompanying commentary disagreed.
The new study is published in the Oct. 6 issue of the New England Journal of Medicine.
Slamon and his colleagues from the Breast Cancer International Research Group tested one of three different treatments in 3,222 women who had HER2-positive early-stage breast cancer. This breast cancer is more aggressive and is linked with a worse outlook and shorter survival times.
One group got a regimen called ACT-- the standard therapy of doxorubicin (Adriamycin) and paraplatin (Carboplatin) followed by docetaxel (Taxotere). A second group got that same standard regimen plus a year of Herceptin -- called ACTH. The third group got the anthracycline-free regimen, called TCH -- doxetaxel (Taxotere) and paraplatin (Carboplatin) with a year of Herceptin.
Herceptin targets HER2, a protein known as human epidermal growth factor receptor 2. In about one of five breast cancers, a gene mutation leads to excess production of HER2 in the cancer cells.
The researchers evaluated disease-free survival and overall survival at five years. The addition of the one year of Herceptin improved both disease-free and overall survival. The disease-free survival rates at five years were 75 percent in the ACT group, 84 percent in the ACTH group and 81 percent in the TCH group.
Overall survival was 87 percent for the ACT group, 92 percent for the ACTH and 91 percent in the TCH group.
However, the rates of congestive heart failure and other cardiac problems were higher in the ACTH group than in the TCH group. Twenty-one of those on ACTH had congestive heart failure, compared with four in the TCH group.
There were fewer reports of side effects such as joint pain and vomiting with the TCH group compared with the ACTH group, Slamon found. "And you get comparable effects," he noted.
Sanofi-Aventis and Genentech (which makes Herceptin) funded the study; Slamon reports receiving honoraria and reimbursement for travel expenses from both companies.
The latest report echoes findings from several previous ones, Slamon said. Doctors have been using the TCH regimen in women at risk for cardiac problems; it is approved by the U.S. Food and Drug Administration. "We're saying it should be used for everybody," Slamon said. "We are saying we think it is the standard of care, with comparable effects, and you lose all the anthracycline toxicity."
However, Dr. Daniel F. Hayes, clinical director of the breast oncology program at the University of Michigan Comprehensive Cancer Center in Ann Arbor, disagreed.
"I think TCH is a standard of care, it's not the standard of care," he said.
"Herceptin itself can cause heart failure," Hayes said. In
the study, there were fewer cases of it in those who got Herceptin without
anthracyclines, but it did still occur.
He suggests a risk-adapted approach, in which a doctor would decide which regimen to use based on a woman's cardiac risk.
Oncologists have had the option of anthracycline-free regimens for a number of years, Hayes noted, although the new study does add some more solid numbers to the outcomes for each regimen.
(SOURCES: Dennis Slamon, M.D., director, clinical and translational research, Jonsson Comprehensive Cancer Center, University of California, Los Angeles; Daniel F. Hayes, M.D., clinical director, breast oncology program, University of Michigan Comprehensive Cancer Center, Ann Arbor; Oct. 6, 2011, New England Journal of Medicine)