Adjuvant Bevacizumab Does Not Improve Survival in HER2-Positive Breast Cancer

According to results from the large randomized BETH trial, bevacizumab did not improve invasive disease-free survival (IDFS) or overall survival (OS) when added to adjuvant therapy for HER2-positive breast cancer.

Photo Courtesy © SABCS/Todd Buchanan 2013

Dennis J. Slamon, MD, PhD

According to results from the large randomized BETH trial, bevacizumab did not improve invasive disease-free survival (IDFS) or overall survival (OS) when added to adjuvant therapy for HER2-positive breast cancer. BETH also showed that an anthracycline-free regimen of TCH (docetaxel, carboplatin, trastuzumab) was at least as effective as a chemotherapy regimen including the anthracycline epirubicin plus trastuzumab as adjuvant treatment of HER2-positive disease. Results from the trial were presented at the 2013 San Antonio Breast Cancer Symposium on Wednesday.

At a median follow-up of 38 months, IDFS was 92% in both TCH arms with and without bevacizumab. In the anthracycline-containing arms, the IDFS was 89% without bevacizumab and 91% with bevacizumab. These differences were numerically different but not statistically significant.

Overall, the OS was 97% for chemotherapy with bevacizumab and 96% for chemotherapy without bevacizumab (HR = 0.87; 95% CI, [0.60-1.25]; log-rankPvalue 0.4387).

“All the antiangiogenic strategies studied [including bevacizumab in the BETH trial] have not impacted survival in breast cancer. Adding bevacizumab does not provide a lot of benefit but does add safety concerns. Unless we can identify a subgroup of patients who will benefit, this strategy is not going anywhere,” said lead author Dennis J. Slamon, MD, PhD, director of Clinical/Translational Research at UCLA Jonsson Comprehensive Cancer Center, Los Angeles, California.

Although the findings for bevacizumab were not confirmatory, the results regarding chemotherapy regimens demonstrate that patients can be effectively treated without the long-term adverse events (AEs) associated with anthracycline therapy, said Slamon. He noted that although anthracyclines are considered a backbone of treatment for breast cancer, including HER2-positive breast cancer, such long-term AEs as congestive heart failure and leukemia are worrisome, especially when combined with trastuzumab.

Trastuzumab combined with anthracyclines increases cardiac toxicity 3- to 5-fold, Slamon explained. “Our new results, which surpassed our expectations, show that it is really not necessary to include an anthracycline as part of the treatment regimen to obtain really ideal results for patients with HER2-positive breast cancer, even if they have a large tumor or node-positive disease,” Slamon said during a press conference where he discussed the findings.

“The importance of these results lies in the fact that TCH has a much better safety profile than anthracycline and trastuzumab combinations and is now equally effective,” he said.

The BETH trial enrolled 3509 women with a median age of approximately 51 years with disease diagnosed as HER2-positive, node-positive, or high-risk node-negative breast cancer. Tumor size was ≤2 cm for half of the patients, and 48% had no positive axillary nodes.

Patients were divided into 2 cohorts. Cohort 1 included 3231 patients randomized to receive TCH or TCH plus bevacizumab; cohort 2 included 278 patients randomized to trastuzumab plus FEC (5-fluorouracil, epirubicin, cyclophosphamide) with or without bevacizumab.

Slamon said that the negative results regarding bevacizumab as part of adjuvant therapy for HER2-positive breast cancer may be partly attributable to the excellent 92% IDFS in the TCH control arm. “It is going to be difficult to develop treatment regimens that have even better response rates than that. While there is some small room for improvement, we now need to concentrate further on improving the safety of adjuvant treatment regimens,” he commented.

Patients enrolled in BETH will be followed prospectively to determine longer-term outcomes. Slamon said that he believes that the TCH regimen is driving the IDFS benefit and he doubted whether bevacizumab would make a significant difference over the longer term.

The study was supported by Roche/Genentech, which develops and markets bevacizumab.

Slamon DJ, Swain SM, Buyse M, et al. Primary results from BETH, a phase 3 controlled study of adjuvant chemotherapy and trastuzumab ±±bevacizumab in patients with HER2-positive, node-positive or high risk node-negative breast cancer. Presented at: 2013 San Antonio Breast Cancer Symposium; December 10-14, 2013; San Antonio, TX. Abstract S1-03.


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