Effects of neoadjuvant chemotherapy with or without zoledronic acid on pathological response: A meta-analysis of randomised trials

Purpose The addition of bisphosphonates to adjuvant therapy improves survival in postmenopausal breast cancer (BC) patients. We report a meta-analysis of four randomised trials of neoadjuvant chemotherapy (CT) +/- zoledronic acid (ZA) in stage II/III BC to investigate the potential for enhancing the pathological response. Methods Individual patient data from four prospective randomised clinical trials reporting the effect of the addition of ZA on the pathological response after neoadjuvant CT were pooled. Primary outcomes were pathological complete response in the breast (PCRb) and in the breast and lymph nodes (PCR). Trial-level and individual patient data meta-analyses were done. Predefined subgroup-analyses were performed for postmenopausal women and patients with triple-negative BC. Results PCRb and PCR data were available in 735 and 552 patients respectively. In the total study population ZA addition to neoadjuvant CT did not increase PCRb or PCR rates. However, in postmenopausal patients, the addition of ZA resulted in a significant, near doubling of the PCRb rate (10.8% for CT only versus 17.7% with CT+ZA; odds ratio [OR] 2.14, 95% confidence interval [CI] 1.01-4.55) and a non-significant benefit of the PCR rate (7.8% for CT only versus 14.6% with CT+ZA; OR 2.62, 95% CI 0.90-7.62). In patients with triple-negative BC a trend was observed favouring CT+ZA. Conclusion This meta-analysis shows no impact from the addition of ZA to neoadjuvant CT on PCR. However, as has been seen in the adjuvant setting, the addition of ZA to neoadjuvant CT may augment the effects of CT in postmenopausal patients with BC.