Combining the chemotherapy drugs docetaxel and carboplatin with the human epidermal growth factor receptor 2 (HER2)-targeted therapy trastuzumab was identified to be an ideal postsurgery treatment option for patients with HER2-positive breast cancer, regardless of tumor size and whether or not disease has spread to the lymph nodes. These results from the BETH study were presented at the 2013 San Antonio Breast Cancer Symposium, December 10-14, 2013.
“Worldwide, anthracyclines such as doxorubicin [Adriamycin] and epirubicin have dominated breast cancer treatment for decades because of a perceived incremental benefit of 3% to 5% in disease-free survival and overall survival that was observed in meta-analysis overview studies that viewed breast cancer as a single disease,” said Dennis J. Slamon, MD, PhD, director of clinical/translational research at the University of California, Los Angeles (UCLA) Jonsson Comprehensive Cancer Center.
“It turns out that anthracyclines were particularly active in the treatment of HER2-positive disease once we applied molecular subtype analyses to breast cancers. These data were derived from treatments used before the development of trastuzumab. In HER2-positive breast cancers, anthracyclines improved outcomes dramatically while adding little or no incremental benefit to the other subtypes that represent 75% to 80% of the disease. Unfortunately, the long-term side effects of anthracyclines in all groups include congestive heart failure and leukemia. We and others have previously shown that adding trastuzumab to anthracycline-based therapy in adjuvant disease increases this cardiac toxicity between three- to five-fold,” Slamon said.
He also explained that their new results showed that it really is not necessary to include an anthracycline as part of the treatment regimen to obtain ideal results for patients with HER2-positive breast cancer. This is true even if the patient has a large tumor or node-positive disease.
“The importance of the results lies in the fact that the TCH [docetaxel, carboplatin, and trastuzumab] combination has a much better safety profile than anthracycline and trastuzumab combinations and is now equally effective,” said Slamon.
This large, randomized, phase III clinical trial evaluated whether adding bevacizumab to postsurgery chemotherapy plus trastuzumab improved outcomes for patients with HER2-positive breast cancer that had spread to the lymph nodes or was highly likely to recur. The researchers called the trial BETH—”bevacizumab and trastuzumab adjuvant therapy in HER2-positive breast cancer.”
A total of 3,509 patients were enrolled in the BETH trial. The majority—3,231 patients—was in cohort 1 and randomly assigned to either TCH or TCH with bevacizumab. Cohort 2 was much smaller, with 278 patients randomly assigned by physicians who elected to use anthracycline-based therapy in addition to trastuzumab, using the anthracycline epirubicin, with or without bevacizumab.
The researchers found that disease-free survival after a median 38-month follow-up was 92% for both arms of the TCH cohort. “These are among the best results we have seen to date in the adjuvant treatment of HER2-positive breast cancer,” Slamon said.