An updated analysis of two large randomized clinical trials has found that breast cancer patients who received the monoclonal antibody trastuzumab (Herceptin) along with chemotherapy are living longer and with less risk of recurrent disease, compared to patients treated with chemotherapy alone.
These studies, sponsored by the National Cancer Institute (NCI), were undertaken to test whether trastuzumab adds to the benefit of adjuvant chemotherapy (doxorubicin, known as Adriamycin, and cyclophosphamide) followed by paclitaxel (Taxol) in women with HER2 + breast cancer who have undergone surgery. Trastuzumab treats the approximately 20 percent of tumors that are HER2 +, that is, their cancer makes too much of the surface protein HER2, which tends to make the cancer grow faster and recur more often than tumors that are not HER2 +.
Four years of follow-up data have concluded that 85.9 percent of 1,989 women treated with trastuzumab are cancer free and 92.6 percent are alive, compared with 73.1 percent and 89.4 percent, respectively, of 1,979 women who were not treated with the monoclonal antibody. In all, 397 patients in the chemotherapy group have developed a recurrent tumor or have died, compared to only 222 in the trastuzumab group.
These results mean that the hazard of disease recurrence is decreased by 52 percent with the addition of trastuzumab to chemotherapy and that trastuzumab therapy was associated with a 35 percent reduction in the risk of death, according to Edith Perez, M.D., director of Mayo Clinic's Multidisciplinary Breast Clinic in Jacksonville, Fla., and primary investigator of one of the trials. She is presenting results of the joint analysis at the annual meeting of the American Society of Clinical Oncology (ASCO).
"Trastuzumab has revolutionized the care of HER2 + breast cancer, and this study clearly shows the statistical and clinical significance of the therapy," says Dr. Perez.
The four-year data show a persistent benefit compared to what was seen at two years, according to Dr. Perez, with trastuzumab combined with chemotherapy continuing to outperform chemotherapy treatment alone. The first joint analysis of these two trials, published Oct. 20, 2005, in the New England Journal of Medicine, showed that at a median of two years after treatment, disease-free survival and overall survival were improved by 52 percent and 33 percent, respectively, with addition of trastuzumab. "The new data are important as they document the continued benefit of the targeted therapy," she says. Targeted therapy uses a specific agent directed against a particular change in a cancer cell.
Researchers also found that the highest risk of relapse occurs within the first two years, and that recurrences continue to occur with longer follow-up. Breast cancer is also more likely to return in patients who were initially diagnosed with larger tumors, or whose cancer was discovered to have spread to a number of lymph nodes, or who had HER2 + cancer that was further sub-typed as estrogen receptor (ER)-negative. So far, 118 patients in the trastuzumab treatment group have developed progressive disease, a second primary cancer or contralateral breast cancer (cancer in the other breast), compared with 243 patients in the chemotherapy group.
In one of the trials (NCCTG-N9831), Dr. Perez reports that the risk of weakened heart muscle was greater in the trastuzumab-treated group compared to patients receiving just chemotherapy (2.5 percent versus 0.2 percent), including cases of congestive heart failure (22 versus 1). But the only cardiac death occurred in the chemotherapy group, she says. "We have learned that cardiac toxicity that might result from trastuzumab can be managed in most cases," she says.
Dr. Perez says that continuing follow-up is needed to continue to define the long-term benefit of using trastuzumab in these patients.
Trastuzumab was approved for the treatment of advanced breast cancer in 1998.
The clinical trials, known as NCCTG-N9831 and NSABP-B-31, were conducted by a network of researchers led by the North Central Cancer Treatment Group (NCCTG) and the National Surgical Adjuvant Breast and Bowel Project (NSABP), in collaboration with the Cancer and Leukemia Group B, the Eastern Cooperative Oncology Group, and the Southwest Oncology Group. Dr. Perez led NCCTG-N9831, as well as the updated analysis.
According to the American Cancer Society, about 178,480 women in the United States will be diagnosed with invasive breast cancer in 2007. About 40,460 women will die from the disease this year. Right now, more than 2 million women living in the United States have been treated for breast cancer.