Addition of Bevacizumab Fails to Improve Invasive Disease-Free Survival vs Adjuvant Chemotherapy/Trastuzumab Alone in HER2-Positive Breast Cancer
Bevacizumab (Avastin) failed to extend invasive disease–free survival when added to trastuzumab (Herceptin)-directed adjuvant chemotherapy in patients with HER2-positive breast cancer in the phase III BETH trial. Although not specifically designed to answer this question, BETH also demonstrated that a non–anthracycline-containing chemotherapy arm was as effective in prolonging survival as an anthracycline-containing arm. The study was presented at the 2013 San Antonio Breast Cancer Symposium (Abstract S1-03).
“Bevacizumab does not add any benefit [as adjuvant therapy] in HER2-positive breast cancer and does add toxicity. Other antiangiogenic strategies studied thus far have not shown a survival benefit. Bevacizumab does not warrant further study unless we can identify a subgroup of patients who benefit,” stated Dennis Slamon, MD, PhD, Director of Clinical/Translational Research at UCLA’s Jonsson Comprehensive Cancer Center and Chief of the Division of Hematology/Oncology at UCLA.
Anthracycline Debate
Experts are divided about whether to abandon anthracyclines. According to Dr. Slamon, a nonanthracycline regimen, such as the one used in BETH, is the best option for HER2-positive early breast cancer based on equivalent efficacy and improved safety. “At our institution, we don’t use anthracyclines,” he said.
Press Conference moderator Jennifer Litton, MD, of MD Anderson Cancer Center said, “We could debate this for 5 hours. I’m on the other side of the aisle on this question, and I don’t think anthracyclines should be thrown away.”
Study Methods
The BETH trial enrolled 3,509 women with HER2-positive, node-positive, or high-risk breast cancer. Cohort 1 included 3,231 women treated with the nonanthracycline regimen of docetaxel, carboplatin, trastuzumab (TCH) with or without bevacizumab followed by trastuzumab with or without bevacizumab for 1 year.
Investigators at about 100 of the centers involved in this large global trial were given the choice of anthracycline or nonanthracycline chemotherapy. Only 278 women were assigned to docetaxel plus trastuzumab with or without bevacizumab followed by fluorouracil, epirubicin, and cyclophosphamide (FEC) followed by trastuzumab with or without bevacizumab (Cohort 2).
No Improvement With Addition of Bevacizumab
No matter which way the data were parsed, bevacizumab did not improve invasive disease–free survival when added to either chemotherapy in cohort 1 or 2.
For the primary endpoint in the overall study population, at 38 months of follow-up, invasive disease–free survival was identical for both arms of the nonanthracycline TCH cohort: 92%. Dr. Slamon said these results leave room for improvement in only a small percentage of patients. “We were struck by this improvement, which was even better than in the BCIRG-006 trial. Our trial is 3.5 times larger than the 006 trial. This is good news for patients,” he commented.
Subgroup analysis according to prespecified stratification factors showed very little difference between subgroups, and results were similar to the overall invasive disease–free survival analysis.
The bevacizumab-containing arms were associated with more hypertension, bleeding, congestive heart failure, proteinuria, and gastrointestinal perforation, as would be expected from other clinical trials. Dr. Slamon said the numbers of patients with these adverse events were low, except for hypertension.
Take-Home Message
In the era before a HER2-directed therapy was developed, HER2-positive breast cancer had a dismal prognosis. “The take-home message from this trial is that we have changed the natural history of HER2-positive breast cancer with HER2-targeted therapies,” Dr. Slamon stated. “The good news for this subtype that traditionally had the worst outcome with a ‘one-size-fits-all’ approach, is that we achieved an invasive disease–free survival of 92% with a nonanthracycline regimen in BETH.”
The study was supported by fund from Roche/Genentech. Dr. Slamon served as an advisor for Roche/Genentech during the time in which the study was conducted.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
