A randomized controlled trial comparing zoledronic acid plus chemotherapy with chemotherapy alone as a neoadjuvant treatment in patients with HER2-negative primary breast cancer.

Abstract

1029 Background: Zoledronic acid (ZOL) has been found to have a synergistic anti-proliferative effect when used in combination with antitumor drugs. We investigated the synergistic effect of ZOL, assessed by pathological complete response (pCR) rate, when added to neoadjuvant chemotherapy (CT) in the primary tumor. Methods: Women with resectable invasive Stage IIA-IIIB breast cancer who are HER2-negative, between 20 and 70 years of age, and ECOG PS 0-1 were eligible. CT regimen was FEC100 q3w × 4 cycles followed by weekly paclitaxel for 12 cycles. ZOL 4mg was administered every 3-4 weeks, a total of 7 times. Patients were randomized 1:1 to the ZOL group or CT group, according to the presence or absence of lymph node metastasis, estrogen receptor (ER) status, and menopausal status. The primary endpoint was the rate of pCR defined as absence of invasive disease in the breast at surgery. The planned sample size was 180 patients. Results: 188 patients were recruited between March 2010 and April 2012; however 10 patients were excluded from the primary assessment. The overall pCR rate was 14.8% and 7.8% in the ZOL and CT groups, respectively (p=0.160). In the postmenopausal patients, pCR rate was 18.4% and 5.4% in the ZOL and CT groups, respectively (p=0.153). In the triple-negative patients, pCR rate was 35.3% and 11.8% in the ZOL and CT groups, respectively (p=0.225). In the postmenopausal and triple-negative patients, pCR rate was 50.0% and 0% in the ZOL and CT groups, respectively (p=0.077). There was no significant difference in severe toxicity between the two groups. Conclusions: The results of this trial suggest that the addition of ZOL to neoadjuvant CT has potential anti-cancer benefit in patients with postmenopausal and triple-negative breast cancer. Further investigation will be warranted. Clinical trial information: 000003261.