SAN ANTONIO—Invasive disease-free survival (DFS) was 92% for patients with HER-2 positive, node-positive or high-risk node-negative breast cancer treated with docetaxel, carboplatin, and trastuzumab with or without bevacizumab, according to results of the phase 3 BETH trial presented at the 2013 San Antonio Breast Cancer Symposium.
“These are among the best results we have seen to date in the adjuvant treatment of HER2-positive breast cancer,” said Dennis J. Slamon, MD, PhD, of UCLA Jonsson Comprehensive Cancer Center and Department of Medicine, Los Angeles, CA. They also mark the next stage in the “treatment evolution” of breast cancer, which has seen rates of DFS increase from 26% with surgery alone to 84% with the introduction of the targeted agents.
“It’s good news for patients who have this subtype of breast cancer,” he added, noting that no longer is the approach to treating the disease “one size fits all.”
The randomized, open-label BETH—bevacizumab with trastuzumab adjuvant therapy in HER2-positive breast cancer—study enrolled 3,509 patients, with the majority in cohort 1 (n = 3,231); cohort 2 included 278 patients.
Patients in cohort 1 were randomly assigned to receive six cycles of docetaxel, carboplatin, and trastuzumab followed by trastuzumab 8 mg/kg intravenous (IV) loading dose and 6 mg/kg IV every 3 weeks thereafter, with or without bevacizumab 15 mg/kg IV every 3 weeks for 1 year after the first dose.
In cohort 2, physicians elected to treat patients with anthracycline-based therapy and administered three cycles of docetaxel/trastuzumab, with or without bevacizumab followed by three cycles of 5-fluorouracil, epirubicin, and cyclophosphamide followed by trastuzumab with or without bevacizumab to complete 1 year of treatment.
Patients had centrally confirmed HER2-positive breast cancer, an Easter Cooperative Oncology Group (ECOG) performance status of 0/1, unilateral invasive breast adenocarcinoma, total mastectomy or lumpectomy, and left ventricular ejection fraction of greater than 55%. Ineligibility criteria included prior therapy with anthracyclines, taxanes, carboplatin, trastuzumab, or bevacizumab for any malignancy; chemotherapy and/or targeted therapy for their current diagnosis of breast cancer; or radiotherapy.
Baseline demographic characteristics were similar between the two treatment arms in cohort 1. Median age was 51.1 years (range, 23-80 years) in the chemotherapy/trastuzumab arm and 51.3 years (range, 21-80 years) in the arm that included bevacizumab; 41% and 40% had undergone breast-conserving surgery, respectively; 48% in each arm had no positive axillary nodes and 59% were hormone receptor–positive.
At a median follow-up of 38 months, in cohort 1, invasive DFS was 92% in both of the study arms (stratified hazard ratio [HR], 1.00; 95% CI: 0.79-1.26; P = 0.9789). In cohort 2, a secondary end point, it was 89% for the chemotherapy/anthracycline/trastuzumab arm compared with 91% for the arm that also included bevacizumab (stratified HR, 0.68; 95% CI: 0.32-1.44; P = 0.3096).
Overall survival, a secondary end point, was 96% in the chemotherapy/trastuzumab arm and 97% in the arm that included bevacizumab (stratified HR, 0.87; 95% CI: 0.60-1.25; log-rank P = 0.4387).
Among patients in cohort 2, DFS was 89%, which was not statistically significant.
“Our new results, which surpassed our expectations, show 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, even if they have a large tumor or have node-positive disease,” said Dr. Slamon.
“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.” The long-term side effects of anthracyclines include congestive heart failure and leukemia.
The study also found that adding bevacizumab to adjuvant chemotherapy with trastuzumab increased toxicity. Grade 3/4 adverse events that were significantly increased in the arm containing bevacizumab included hypertension (P < 0.0001), bleeding (P < 0.0001), congestive heart failure (P = 0.0621), proteinuria (P < 0.0001), and gastrointestinal perforations (P = 0.0031).
Patients will continue to be followed to determine whether long-term outcomes remain similar between the two arms of cohorts 1 and 2.
“While there is some small room for improvement, we now need to further concentrate on improving the safety of adjuvant treatment regimens,” Dr. Slamon concluded.
- Slamon DJ et al. S1-03. Presented at: San Antonio Breast Cancer Symposium 2013. Dec. 10-14, 2013; San Antonio.