These are the encouraging findings in an interim report from HERA, an ongoing large, international clinical trial of Herceptin, being published today in the New England Journal of Medicine. The analysis was led by Richard Gelber, PhD, of Dana-Farber Cancer Institute, who led the statistical analysis for the HERA trial, which is one of the largest breast cancer trials to date. It includes more than 5,000 patients in 39 countries.
Women whose tumors were HER2-positive – that is, overexpressing a protein associated with more aggressive cancer and poorer outcomes – had approximately a 50 percent lower risk of disease recurrence. This translated into an 8 percent improvement in the number of women who were free of disease two years after beginning the treatment.
"This is probably the biggest evidence of a treatment effect I've ever seen in oncology," says Gelber. "It is quite remarkable." Harold Burstein, MD, PhD, of Dana-Farber, wrote in a commentary published with the report that the results have "a profound lesson: not all breast cancers are the same." The study shows the success of therapy tailored to a specific biological form of the disease."Now we have made dramatic progress for patients with HER2-positive breast tumors, who now have a much lower risk of recurrence and better chance of survival because of trastuzumab," says Burstein.
The interim data were released last May at the annual meeting of the American Society of Clinical Oncology, prompting standing ovations from cancer specialist attending the conference.
Herceptin is a monoclonal antibody-based drug developed specifically to block the activity of the HER2 protein, a growth factor receptor that is overexpressed on cancer cells of an estimated 20 to 30 percent of breast cancer patients. HER2-positive tumors, which can be identified with a test when the breast cancer diagnosis is made, are generally more aggressive and prone to spreading, and are resistant to many chemotherapy agents.
The HERA trial, sponsored by Roche, the manufacturer of Herceptin, and carried out by the Breast International Group (BIG), a federation of international breast cancer clinical trial cooperative groups, began enrolling patients in 2001. The aim is to determine whether Herceptin treatment improves outcomes in early HER2- positive breast cancer when added to standard chemotherapy. More than 5,000 women had surgery and various types of chemotherapy drugs before entering the trial. About two-thirds had cancer that had spread to the underarm lymph nodes.
One group of 1,694 patients received Herceptin every three weeks for one year; another 1,694 received it for two years. No Herceptin was administered to the third group of 1,693 patients.
Recurrences in HER2-positive breast cancer tend to happen in the first year or two. When the statisticians took their first look at the data after one year, the benefits in the Herceptin group were already apparent. "The differences showed up so quickly that the Data Monitoring Committee felt that data had to be released, even though we don't know the long term effects and the long term side effects," says Gelber.
There were 220 recurrences in the group that did not receive Herceptin, compared with 127 in the group treated for one year with Herceptin. The group receiving the drug had a significant improvement in disease-free survival of 8.4 percent at two years. Disease-free survival is the length of time after treatment during which patients show no signs of the disease. Overall survival in the groups did not differ by a statistically significant amount, but that could change as the study continues, the researchers say. The study is planned to run through 2008.
The researchers were gratified to discover that only 0.5 percent of the patients receiving Herceptin had serious cardiac side effects. It was a concern because in previous trials combining chemotherapy with Herceptin the rate had been significantly higher. The scientists said that the lower incidence of cardiac side effects in the HERA Trial may be related to the facts that Herceptin was administered after chemotherapy treatment had been completed, instead of simultaneously, and that patients with insufficient cardiac function after chemotherapy were not included.
The journal also published results of two other Herceptin trials among North American patients, with similar findings of effectiveness.
Dana-Farber Cancer Institute (www.dana-farber.org) is a principal teaching affiliate of the Harvard Medical School and is among the leading cancer research and care centers in the United States. It is a founding member of the Dana-Farber/Harvard Cancer Center (DF/HCC), designated a comprehensive cancer center by the National Cancer Institute.
Journal
New England Journal of Medicine