Bevacizumab improved pathological, clinical response rates in metastatic breast cancer

Issue: July 10, 2011

2011 ASCO Annual Meeting

CHICAGO — In results from NSABP protocol B-40 presented here today, Harry D. Bear, MD, PhD, said that the addition of bevacizumab to neoadjuvant chemotherapy improved both pathologic and clinical complete response in women with operable HER-2 negative breast cancer.

Bear, chairman of surgical oncology and professor of microbiology and immunology at Virginia Commonwealth University School of Medicine, presented the results at the 2011 ASCO Annual Meeting. Unlike bevacizumab (Avastin, Genentech), the addition of either capecitabine (Xeloda, Hoffman LaRoche) or gemcitabine (Gemzar, Eli Lilly) to docetaxel-based chemotherapy increased toxicity without improving response rates.

“Neither capecitabine nor gemcitabine added to docetaxel increased clinical or pathologic response rates in the neoadjuvant setting, although they did increase toxicities,” he said. “Bevacizumab, on the other hand, added to regimens based on docetaxel followed by AC significantly increased both clinical and pathologic complete response rates.”

Patients in the trial (n=1,206) were assigned to docetaxel/doxorubicin/cyclophosphamide alone as a control (n=396). Patients in the experimental groups were assigned to that chemotherapy regime plus capecitabine (n=399) or gemcitabine (n=396). Half of patients were then assigned to four cycles of preoperative doxorubicin/cyclophosphamide with bevacizumab. The remainder were assigned to four cycles of preoperative doxorubicin/cyclophosphamide without bevacizumab. The group assigned to bevacizumab received another 10 doses after surgery.

Bevacizumab was associated with an increased rate of pathologic complete response (28.4% vs. 34.5%) and clinical complete response (55.8% vs. 64.3%) compared with the non-bevacizumab group (OR=1.33). Bear said the effect was particularly pronounced in patients with HR-positive tumors, 15.2% vs. 23.3% (OR=1.7).

Bear said there was an absolute and statistically significant 8.5% increase in the incidence of clinical complete response for patients in the bevacizumab group. The effect was even greater in HR-positive patients, with an 11% absolute increase.

Bevacizumab was also associated with a statistically insignificant increase in pathologic complete response in the breast and lymph nodes. However, the increase was statistically significant in patients with HR-positive tumors (OR=1.59).

However, patients treated with gemcitabine or capecitabine did not experience the same positive results as those treated with bevacizumab. The rate of complete response in the breast was 29.7% for capecitabine and 32.7% for gemcitabine vs. 29.7% for the control arm. Bear said there was no statistically significant difference between the treatments. Additionally, the rate of pathologic complete response in the breast and lymph nodes was 23.3% in the capecitabine arm and 27.3% in the gemcitabine arm vs. 26.0% in the control arm.

Neither capecitabine (58.3%) nor gemcitabine (60.4%) increased clinical complete response rates compared with docetaxel alone (61.5%). Bear added that patients in both the capecitabine and gemcitabine arms experienced increased grade-3/grade-4 adverse events.

“In this case of gemcitabine, this was mostly accounted for by an increase in the incidence of grade-3/grade-4 neutropenia, and for capecitabine, mostly by an increase in hand-foot syndrome,” he said. – by Jason Harris

For more information:

Bear HD. #LBA1005. Presented at: 2011 ASCO Annual Meeting; Chicago; June 3-7, 2011.

Disclosure: Dr. Bear reported receiving honoraria from Genentech and Roche.

Follow HemOncToday.com on Twitter.