David Cameron, MD
Patients with triple-negative breast cancer had no statistically significant improvement in disease-free survival when they received adjuvant treatment with chemotherapy plus 1 year of bevacizumab compared with patients who received chemotherapy alone, according to the results of the phase III BEATRICE trial presented at the 35th Annual San Antonio Breast Cancer Symposium.
In the open-label, multinational, BEATRICE trial, 2591 patients with resected triple-negative invasive early breast cancer were randomized to receive the investigator’s choice of either standard chemotherapy for four to eight cycles followed by observation (n = 1290) or bevacizumab (5 mg/kg/week equivalent) plus investigator’s choice of standard chemotherapy for 4 to 8 cycles followed by bevacizumab monotherapy for a total of one year (n = 1301). Researchers were allowed to use taxane-based chemotherapy (>
4 cycles), anthracycline-based chemotherapy (>
4 cycles), or anthracycline and taxane chemotherapy (3-4 cycles each). Patients were recruited between December 2007 and March 2010. The primary endpoint of the trial was invasive disease-free survival (IDFS).
“This endpoint includes other invasive cancers, just as a check to make sure that we’re not inducing cancer in another area,” said David Cameron, MD, professor of Oncology at Edinburgh University in Scotland and lead author of the study.
After a median follow-up of 31.5 months in the chemotherapy alone arm and 32 months in the bevacizumab arm, the 3-year IDFS rate in the bevacizumab arm was 83.7% (95% CI, 81.4-86.0) compared with 82.7% (95% CI, 80.5-85.0) in the chemotherapy arm (stratified hazard ratio [HR] = 0.87; 95% CI, 0.72-1.07; P = .
1810). An interim analysis of overall survival (OS) was also performed, although only 59% of the required number of events had occurred, so the data was not considered mature. In the bevacizumab arm, 93 deaths had occurred during follow-up compared with 107 deaths in the chemotherapy arm (stratified HR = 0.84; 95% CI, 0.64-1.12; P
The adverse events observed in this trial are consistent with what has been observed in other trials that have studied the use of bevacizumab in metastatic breast cancer, Cameron said. Certain grade >
3 adverse events appeared more frequently in the bevacizumab arm than the chemotherapy arm, including hypertension (88 [7%] versus 6 [<1%], respectively), a side effect that has been associated with bevacizumab use in past studies. Left ventricular dysfunction and clinical heart failure were also clinically relevant adverse events that appeared more commonly when bevacizumab was used, although these adverse events were resolved more quickly in the bevacizumab arm compared with the chemotherapy arm.
“The good news for women is that the outcome of 84% invasive disease-free survival after three years was actually much better than we had originally planned,” Cameron said. “When women go onto the Web and look up what is a very negative image of triple-negative breast cancer, we can at least say [according to] a big worldwide phase III trial, actually the outcomes maybe are not as bad as the older literature suggests. But in terms of an improvement in outcome, one year of bevacizumab isn’t the answer.”
Cameron noted that further follow-up is required to determine whether bevacizumab has any potential to improve OS. The prespecified OS analysis will be performed when 340 patients in the study have died or all patients have been followed for a median of 5 years, whichever comes first. Cameron said the results are estimated to become available in late 2013.
Cameron D, Brown J, Dent R, et al. Primary results of BEATRICE, a randomized phase III trial evaluating adjuvant bevacizumab-containing therapy in triple-negative breast cancer. Presented at: 2012 CTRC-AACR San Antonio Breast Cancer Symposium; December 4-8, 2012; San Antonio, Texas. Abstract S6-5.
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