A randomized, double-blind, phase II, exploratory trial evaluating the palliative benefit of either continuing pamidronate or switching to zoledronic acid in patients with high-risk bone metastases from breast cancer

Breast Cancer Res Treat. 2016 Jan;155(1):77-84. doi: 10.1007/s10549-015-3646-2. Epub 2015 Dec 7.

Abstract

Previous studies suggest switching from pamidronate to a more potent bone-targeted agent is associated with biomarker and palliative response in breast cancer patients with bone metastases. Until now, this has not been addressed in a double-blind, randomized trial. Breast cancer patients with high-risk bone metastases, despite >3 months of pamidronate, were randomized to either continue pamidronate or switch to zoledronic acid every 4 weeks for 12 weeks. Primary outcome was the proportion of patients achieving a fall in serum C-telopeptide (sCTx) at 12 weeks. Secondary outcomes included difference in mean sCTx, pain scores, quality of life, toxicity, and skeletal-related events (SREs). Seventy-three patients entered the study; median age 61 years (range 37-87). Proportion of patients achieving a fall in sCTx over the 12-week evaluation period was 26/32 (81 %) with zoledronic acid and 18/29 (62 %) with pamidronate (p = 0.095). Mean decrease in sCTx (mean difference between groups = 50 ng/L, 95 % CI 18-84; p = 0.003) was significantly greater in patients who received zoledronic acid. Quality of life, pain scores, toxicity, and frequency of new SREs were comparable between the two arms. While a switch from pamidronate to zoledronic acid resulted in reduction in mean sCTx, there were no significant differences between the arms for proportion of patients achieving a reduction in sCTx, quality of life, pain scores, toxicity or SREs. Given the lack of palliative improvement, the current data do not support a switching strategy.

Keywords: Bisphosphonate; Bone metastasis; Breast cancer; Pamidronate; Zoledronic acid.

Publication types

  • Clinical Trial, Phase II
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use
  • Bone Density Conservation Agents / administration & dosage
  • Bone Density Conservation Agents / adverse effects
  • Bone Density Conservation Agents / therapeutic use
  • Bone Neoplasms / drug therapy*
  • Bone Neoplasms / secondary*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / pathology*
  • Combined Modality Therapy
  • Diphosphonates / administration & dosage
  • Diphosphonates / adverse effects
  • Diphosphonates / therapeutic use*
  • Drug Substitution
  • Female
  • Humans
  • Imidazoles / administration & dosage
  • Imidazoles / adverse effects
  • Imidazoles / therapeutic use*
  • Middle Aged
  • Palliative Care*
  • Pamidronate
  • Quality of Life
  • Treatment Outcome
  • Zoledronic Acid

Substances

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