Zoledronate for patients with invasive residual disease after anthracyclines-taxane-based chemotherapy for early breast cancer – The Phase III NeoAdjuvant Trial Add-oN (NaTaN) study (GBG 36/ABCSG 29)

Background Patients with invasive residual disease after neoadjuvant chemotherapy (NACT) are considered to have chemo-resistant breast cancer. Bisphosphonates are an established treatment for bone metastases and are of potential benefit as adjuvant treatment in early breast cancer. Patients and methods Patients who had invasive tumour residuals (ypT1-4 and/or ypN+) after a minimum of four cycles of anthracycline-taxane-containing NACT were eligible for the NeoAdjuvant Trial Add-oN study. Patients were randomised within 3 years after surgery to receive zoledronate 4 mg i.v. for 5 years versus observation. Zoledronate was given every 4 weeks for the first 6 months, every 3 months for the following 2 years, and every 6 months for the last 2.5 years. Primary objective was disease-free survival. Results After a median time of 54.7 months no difference in disease-free survival was observed between the zoledronate and observation groups (hazard ratio [HR] 0.960, 95% confidence interval [CI] 0.709–1.30, log rank P=0.789). Various subgroups were examined without identifying a treatment effect of zoledronate. Patients over 55 years of age showed a HR of 0.832 in favour of zoledronate, but the result was not significant (P=0.480). A similar result was obtained for overall survival with a HR of 1.19 (95% CI 0.79–1.79; log rank P=0.408). Zoledronate was well tolerated and no new toxicity signal was identified. Conclusion Postneoadjuvant treatment with zoledronate does not improve outcome in patients without pathological complete response after neoadjuvant anthracycline-taxane-based chemotherapy for early breast cancer.