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)

Eur J Cancer. 2016 Sep:64:12-21. doi: 10.1016/j.ejca.2016.05.015. Epub 2016 Jun 17.

Abstract

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.

Keywords: Adjuvant treatment; Early breast cancer; Postneoadjuvant; Zoledronate.

Publication types

  • Clinical Trial, Phase III
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents / therapeutic use*
  • Bone Density Conservation Agents / therapeutic use*
  • Bone Neoplasms / prevention & control*
  • Bone Neoplasms / secondary*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / pathology
  • Chemotherapy, Adjuvant
  • Diphosphonates / therapeutic use*
  • Disease-Free Survival
  • Female
  • Humans
  • Imidazoles / therapeutic use*
  • Middle Aged
  • Neoplasm, Residual
  • Zoledronic Acid

Substances

  • Antineoplastic Agents
  • Bone Density Conservation Agents
  • Diphosphonates
  • Imidazoles
  • Zoledronic Acid